Insulin-Like Growth Factor (IGF) Pathway Targeting in Cancer: Role of the IGF Axis and Opportunities for Future Combination Studies

Despite a strong preclinical rationale for targeting the insulin-like growth factor (IGF) axis in cancer, clinical studies of IGF-1 receptor (IGF-1R)-targeted monotherapies have been largely disappointing, and any potential success has been limited by the lack of validated predictive biomarkers for...

Celý popis

Uloženo v:
Podrobná bibliografie
Vydáno v:Targeted oncology Ročník 12; číslo 5; s. 571 - 597
Hlavní autoři: Simpson, Aaron, Petnga, Wilfride, Macaulay, Valentine M., Weyer-Czernilofsky, Ulrike, Bogenrieder, Thomas
Médium: Journal Article
Jazyk:angličtina
Vydáno: Cham Springer International Publishing 01.10.2017
Springer Nature B.V
Témata:
Antineoplastic Agents - pharmacology
Biomedicine
Cancer
Drug Resistance, Neoplasm - physiology
Humans
Insulin
Insulin-like growth factors
Ligands
Medicine
Medicine & Public Health
Metabolism
Neoplasms - drug therapy
Oncology
Receptor, IGF Type 1 - antagonists & inhibitors
Review
Review Article
Targeted cancer therapy
Treatment resistance
ISSN:1776-2596, 1776-260X, 1776-260X
On-line přístup:Získat plný text
Tagy: Přidat tag
Žádné tagy, Buďte první, kdo vytvoří štítek k tomuto záznamu!
Abstract Despite a strong preclinical rationale for targeting the insulin-like growth factor (IGF) axis in cancer, clinical studies of IGF-1 receptor (IGF-1R)-targeted monotherapies have been largely disappointing, and any potential success has been limited by the lack of validated predictive biomarkers for patient enrichment. A large body of preclinical evidence suggests that the key role of the IGF axis in cancer is in driving treatment resistance, via general proliferative/survival mechanisms, interactions with other mitogenic signaling networks, and class-specific mechanisms such as DNA damage repair. Consequently, combining IGF-targeted agents with standard cytotoxic agents, other targeted agents, endocrine therapies, or immunotherapies represents an attractive therapeutic approach. Anti-IGF-1R monoclonal antibodies (mAbs) do not inhibit IGF ligand 2 (IGF-2) activation of the insulin receptor isoform-A (INSR-A), which may limit their anti-proliferative activity. In addition, due to their lack of specificity, IGF-1R tyrosine kinase inhibitors are associated with hyperglycemia as a result of interference with signaling through the classical metabolic INSR-B isoform; this may preclude their use at clinically effective doses. Conversely, IGF-1/IGF-2 ligand-neutralizing mAbs inhibit proliferative/anti-apoptotic signaling via IGF-1R and INSR-A, without compromising the metabolic function of INSR-B. Therefore, combination regimens that include these agents may be more efficacious and tolerable versus IGF-1R-targeted combinations. Herein, we review the preclinical and clinical experience with IGF-targeted therapies to-date, and discuss the rationale for future combination approaches as a means to overcome treatment resistance.
AbstractList Despite a strong preclinical rationale for targeting the insulin-like growth factor (IGF) axis in cancer, clinical studies of IGF-1 receptor (IGF-1R)-targeted monotherapies have been largely disappointing, and any potential success has been limited by the lack of validated predictive biomarkers for patient enrichment. A large body of preclinical evidence suggests that the key role of the IGF axis in cancer is in driving treatment resistance, via general proliferative/survival mechanisms, interactions with other mitogenic signaling networks, and class-specific mechanisms such as DNA damage repair. Consequently, combining IGF-targeted agents with standard cytotoxic agents, other targeted agents, endocrine therapies, or immunotherapies represents an attractive therapeutic approach. Anti-IGF-1R monoclonal antibodies (mAbs) do not inhibit IGF ligand 2 (IGF-2) activation of the insulin receptor isoform-A (INSR-A), which may limit their anti-proliferative activity. In addition, due to their lack of specificity, IGF-1R tyrosine kinase inhibitors are associated with hyperglycemia as a result of interference with signaling through the classical metabolic INSR-B isoform; this may preclude their use at clinically effective doses. Conversely, IGF-1/IGF-2 ligand-neutralizing mAbs inhibit proliferative/anti-apoptotic signaling via IGF-1R and INSR-A, without compromising the metabolic function of INSR-B. Therefore, combination regimens that include these agents may be more efficacious and tolerable versus IGF-1R-targeted combinations. Herein, we review the preclinical and clinical experience with IGF-targeted therapies to-date, and discuss the rationale for future combination approaches as a means to overcome treatment resistance.
Despite a strong preclinical rationale for targeting the insulin-like growth factor (IGF) axis in cancer, clinical studies of IGF-1 receptor (IGF-1R)-targeted monotherapies have been largely disappointing, and any potential success has been limited by the lack of validated predictive biomarkers for patient enrichment. A large body of preclinical evidence suggests that the key role of the IGF axis in cancer is in driving treatment resistance, via general proliferative/survival mechanisms, interactions with other mitogenic signaling networks, and class-specific mechanisms such as DNA damage repair. Consequently, combining IGF-targeted agents with standard cytotoxic agents, other targeted agents, endocrine therapies, or immunotherapies represents an attractive therapeutic approach. Anti-IGF-1R monoclonal antibodies (mAbs) do not inhibit IGF ligand 2 (IGF-2) activation of the insulin receptor isoform-A (INSR-A), which may limit their anti-proliferative activity. In addition, due to their lack of specificity, IGF-1R tyrosine kinase inhibitors are associated with hyperglycemia as a result of interference with signaling through the classical metabolic INSR-B isoform; this may preclude their use at clinically effective doses. Conversely, IGF-1/IGF-2 ligand-neutralizing mAbs inhibit proliferative/anti-apoptotic signaling via IGF-1R and INSR-A, without compromising the metabolic function of INSR-B. Therefore, combination regimens that include these agents may be more efficacious and tolerable versus IGF-1R-targeted combinations. Herein, we review the preclinical and clinical experience with IGF-targeted therapies to-date, and discuss the rationale for future combination approaches as a means to overcome treatment resistance.[Figure not available: see fulltext.]
Despite a strong preclinical rationale for targeting the insulin-like growth factor (IGF) axis in cancer, clinical studies of IGF-1 receptor (IGF-1R)-targeted monotherapies have been largely disappointing, and any potential success has been limited by the lack of validated predictive biomarkers for patient enrichment. A large body of preclinical evidence suggests that the key role of the IGF axis in cancer is in driving treatment resistance, via general proliferative/survival mechanisms, interactions with other mitogenic signaling networks, and class-specific mechanisms such as DNA damage repair. Consequently, combining IGF-targeted agents with standard cytotoxic agents, other targeted agents, endocrine therapies, or immunotherapies represents an attractive therapeutic approach. Anti-IGF-1R monoclonal antibodies (mAbs) do not inhibit IGF ligand 2 (IGF-2) activation of the insulin receptor isoform-A (INSR-A), which may limit their anti-proliferative activity. In addition, due to their lack of specificity, IGF-1R tyrosine kinase inhibitors are associated with hyperglycemia as a result of interference with signaling through the classical metabolic INSR-B isoform; this may preclude their use at clinically effective doses. Conversely, IGF-1/IGF-2 ligand-neutralizing mAbs inhibit proliferative/anti-apoptotic signaling via IGF-1R and INSR-A, without compromising the metabolic function of INSR-B. Therefore, combination regimens that include these agents may be more efficacious and tolerable versus IGF-1R-targeted combinations. Herein, we review the preclinical and clinical experience with IGF-targeted therapies to-date, and discuss the rationale for future combination approaches as a means to overcome treatment resistance.Despite a strong preclinical rationale for targeting the insulin-like growth factor (IGF) axis in cancer, clinical studies of IGF-1 receptor (IGF-1R)-targeted monotherapies have been largely disappointing, and any potential success has been limited by the lack of validated predictive biomarkers for patient enrichment. A large body of preclinical evidence suggests that the key role of the IGF axis in cancer is in driving treatment resistance, via general proliferative/survival mechanisms, interactions with other mitogenic signaling networks, and class-specific mechanisms such as DNA damage repair. Consequently, combining IGF-targeted agents with standard cytotoxic agents, other targeted agents, endocrine therapies, or immunotherapies represents an attractive therapeutic approach. Anti-IGF-1R monoclonal antibodies (mAbs) do not inhibit IGF ligand 2 (IGF-2) activation of the insulin receptor isoform-A (INSR-A), which may limit their anti-proliferative activity. In addition, due to their lack of specificity, IGF-1R tyrosine kinase inhibitors are associated with hyperglycemia as a result of interference with signaling through the classical metabolic INSR-B isoform; this may preclude their use at clinically effective doses. Conversely, IGF-1/IGF-2 ligand-neutralizing mAbs inhibit proliferative/anti-apoptotic signaling via IGF-1R and INSR-A, without compromising the metabolic function of INSR-B. Therefore, combination regimens that include these agents may be more efficacious and tolerable versus IGF-1R-targeted combinations. Herein, we review the preclinical and clinical experience with IGF-targeted therapies to-date, and discuss the rationale for future combination approaches as a means to overcome treatment resistance.
Author Macaulay, Valentine M.
Petnga, Wilfride
Weyer-Czernilofsky, Ulrike
Simpson, Aaron
Bogenrieder, Thomas
Author_xml – sequence: 1
  givenname: Aaron
  surname: Simpson
  fullname: Simpson, Aaron
  organization: Department of Oncology, University of Oxford
– sequence: 2
  givenname: Wilfride
  surname: Petnga
  fullname: Petnga, Wilfride
  organization: Department of Oncology, University of Oxford
– sequence: 3
  givenname: Valentine M.
  surname: Macaulay
  fullname: Macaulay, Valentine M.
  organization: Department of Oncology, University of Oxford
– sequence: 4
  givenname: Ulrike
  surname: Weyer-Czernilofsky
  fullname: Weyer-Czernilofsky, Ulrike
  organization: Boehringer Ingelheim RCV
– sequence: 5
  givenname: Thomas
  surname: Bogenrieder
  fullname: Bogenrieder, Thomas
  email: thomas.bogenrieder@boehringer-ingelheim.com
  organization: Boehringer Ingelheim RCV, Department of Urology, University Hospital Grosshadern, Ludwig-Maximilians-University
BackLink https://www.ncbi.nlm.nih.gov/pubmed/28815409$$D View this record in MEDLINE/PubMed
BookMark eNp9kl9rFDEUxYNU7B_9AL5IwJf6MJpMJsmMD0JZ3HVhoaIVfAuZmZvd1Nlkm2Rs-9wvbtbtSi3oUwL3dw7nJucYHTjvAKGXlLylhMh3kVJesoJQWRBOq4I_QUdUSlGUgnw_2N95Iw7RcYyXhFSy5OQZOizrmvKKNEfobu7iOFhXLOwPwLPgr9MKT3WXfMCn89n0Df6s0-pa3-ILHZaQrFti6_BEuw7Ce_zFD4C9wWkFONP47MZGrF2PzzcbH9LobLIQsclu0zGNAfDEr1vrdLLe4a9p7PP4OXpq9BDhxf15gr5NP15MPhWL89l8crYoOs5EKkzNDG_yAoLRvH5bt1JTIyXrDUjgpa6brmeVobIlwkjNpSmho4ywhvZVVbET9GHnuxnbNfQduBT0oDbBrnW4VV5b9ffE2ZVa-p-KC0qEaLLB6b1B8FcjxKTWNnYwDNqBH6OiDSNVLQgXGX39CL30Y3B5vUxVtG4kbbbUq4eJ_kTZ_08G5A7ogo8xgFGdTb8fLwe0g6JEbZugdk1QuQlq2wTFs5I-Uu7N_6cpd5qYWbeE8CD0P0W_AM9FxL8
CitedBy_id crossref_primary_10_1158_0008_5472_CAN_20_2860
crossref_primary_10_1038_s41416_019_0677_1
crossref_primary_10_1038_s41416_020_0774_1
crossref_primary_10_3389_fonc_2020_612385
crossref_primary_10_3390_cancers16183175
crossref_primary_10_3390_ijms20174267
crossref_primary_10_3389_fendo_2023_1291812
crossref_primary_10_2174_1874467215666220103111009
crossref_primary_10_3390_ijms26115204
crossref_primary_10_1038_s41388_019_0694_9
crossref_primary_10_3390_ijms22095019
crossref_primary_10_1080_13543784_2019_1694660
crossref_primary_10_1002_bco2_187
crossref_primary_10_1038_s41416_021_01393_y
crossref_primary_10_1007_s12672_018_0352_7
crossref_primary_10_3389_fendo_2020_620013
crossref_primary_10_3390_jpm14030255
crossref_primary_10_3389_fgene_2021_670240
crossref_primary_10_1002_jcb_28111
crossref_primary_10_3389_fendo_2023_1081831
crossref_primary_10_37349_emed_2025_1001342
crossref_primary_10_1038_s41388_021_01907_1
crossref_primary_10_3389_fendo_2024_1396192
crossref_primary_10_3390_ijms25168854
crossref_primary_10_1016_j_ghir_2020_101343
crossref_primary_10_1016_j_anai_2020_12_005
crossref_primary_10_1007_s00381_020_04692_6
crossref_primary_10_1016_j_jtocrr_2021_100206
crossref_primary_10_3389_fcell_2021_630503
crossref_primary_10_3390_cells10082075
crossref_primary_10_1038_s41467_020_18442_4
crossref_primary_10_3390_medsci9030048
crossref_primary_10_1016_j_pharmthera_2020_107502
crossref_primary_10_1111_cas_15231
crossref_primary_10_1186_s13046_023_02623_2
crossref_primary_10_4093_dmj_2021_0077
crossref_primary_10_1002_jcp_27742
crossref_primary_10_1002_ppul_26780
crossref_primary_10_1007_s10911_022_09511_z
crossref_primary_10_3390_cells8091017
crossref_primary_10_1016_j_bbcan_2021_188598
crossref_primary_10_3390_ijms21114030
crossref_primary_10_33549_physiolres_934631
crossref_primary_10_3389_fonc_2022_1055589
crossref_primary_10_3390_cells8080895
crossref_primary_10_1007_s00292_020_00763_2
crossref_primary_10_3390_ijms20123027
crossref_primary_10_3390_ijms20184440
crossref_primary_10_1038_s41467_022_34391_6
crossref_primary_10_1186_s13058_020_01382_8
crossref_primary_10_1177_03009858231207021
crossref_primary_10_3390_cells8111318
crossref_primary_10_3390_ijms20194915
crossref_primary_10_1158_1078_0432_CCR_21_1096
crossref_primary_10_3390_ijms22041831
crossref_primary_10_3390_ijms231810382
crossref_primary_10_1097_MD_0000000000022890
crossref_primary_10_3389_fendo_2020_00435
crossref_primary_10_1186_s13058_023_01649_w
crossref_primary_10_1111_andr_12658
crossref_primary_10_1016_j_critrevonc_2025_104764
crossref_primary_10_1002_bmm2_12069
crossref_primary_10_1093_jnci_djaf140
crossref_primary_10_1038_s41388_021_01868_5
crossref_primary_10_1016_j_critrevonc_2025_104809
crossref_primary_10_1158_1078_0432_CCR_18_2697
crossref_primary_10_3390_ijms21196995
crossref_primary_10_1038_s41416_024_02713_8
crossref_primary_10_3390_ijms25179302
crossref_primary_10_3389_fimmu_2022_998244
crossref_primary_10_4158_EP_2019_0353
crossref_primary_10_3390_cancers11040517
crossref_primary_10_3390_cells8121499
crossref_primary_10_1016_j_apsb_2019_12_010
crossref_primary_10_1111_pin_13080
crossref_primary_10_1080_13880209_2020_1839511
crossref_primary_10_1017_S1460396919000955
crossref_primary_10_3390_cancers12123568
crossref_primary_10_1016_j_omtn_2019_02_008
crossref_primary_10_1158_1541_7786_MCR_21_0961
crossref_primary_10_3389_fonc_2023_1140133
crossref_primary_10_3390_cancers13102478
crossref_primary_10_3892_etm_2018_5783
crossref_primary_10_3390_ijms241914882
crossref_primary_10_1242_jcs_260014
crossref_primary_10_1371_journal_pone_0204173
crossref_primary_10_1007_s12070_025_06008_z
crossref_primary_10_1158_0008_5472_CAN_22_0363
crossref_primary_10_3390_ani15030444
crossref_primary_10_3390_cancers14153591
crossref_primary_10_3390_cancers11081185
crossref_primary_10_1016_j_mayocp_2020_03_037
crossref_primary_10_3389_fendo_2021_701246
crossref_primary_10_1016_j_crmeth_2022_100338
crossref_primary_10_30621_jbachs_854439
crossref_primary_10_3389_fonc_2025_1540426
crossref_primary_10_3389_fimmu_2020_01986
crossref_primary_10_3390_cancers13081781
crossref_primary_10_1158_1541_7786_MCR_21_0038
crossref_primary_10_1007_s12672_021_00407_8
crossref_primary_10_3390_ijms22063280
crossref_primary_10_46879_ukroj_3_2022_79_92
crossref_primary_10_1371_journal_pcbi_1009125
crossref_primary_10_3390_ijerph19031116
crossref_primary_10_1039_D1FO03283F
crossref_primary_10_3389_fonc_2021_626577
crossref_primary_10_3390_biom11020217
crossref_primary_10_3390_ijms20133258
Cites_doi 10.1038/nature08768
10.1016/j.gendis.2014.10.004
10.1158/1535-7163.MCT-12-0618
10.3389/fendo.2014.00010
10.1093/annonc/mdq349
10.1200/jco.2014.32.15_suppl.2617
10.1002/(SICI)1096-9098(199809)69:1<21::AID-JSO5>3.0.CO;2-M
10.1038/nm.3667
10.1634/theoncologist.2016-0220
10.15252/emmm.201303376
10.1158/1078-0432.CCR-12-1840
10.1007/s11523-012-0248-3
10.1002/cncr.28728
10.1038/onc.2016.248
10.1111/cei.12374
10.1016/j.ccell.2014.11.008
10.1002/jcp.24217
10.1158/1535-7163.MCT-13-0442-T
10.1158/1078-0432.CCR-14-0940
10.1056/NEJMoa1501824
10.1038/onc.2015.488
10.1073/pnas.92.26.12146
10.1126/science.aad3018
10.1038/bjc.2015.242
10.1172/JCI41824
10.1038/srep06855
10.1016/j.beem.2008.08.004
10.1186/1471-2407-13-41
10.1158/1535-7163.MCT-05-0048
10.1530/ERC-15-0002
10.1101/gad.7.3.331
10.1002/pbc.25334
10.1158/1078-0432.CCR-15-1677
10.1016/j.radonc.2012.03.009
10.1158/0008-5472.CAN-05-3126
10.1038/nrc3215
10.1200/JCO.2011.37.4355
10.1002/stem.1328
10.1158/0008-5472.CAN-13-2923
10.1002/cncr.27459
10.1053/j.gastro.2016.09.001
10.1007/s00018-013-1514-y
10.1200/JCO.2011.37.2359
10.1016/j.cllc.2016.07.007
10.1158/1535-7163.MCT-08-1171
10.1093/jnci/djv258
10.1126/science.8418502
10.1158/1078-0432.CCR-07-4879
10.1200/jco.2010.28.15_suppl.3104
10.1126/scisignal.2000628
10.1158/2159-8290.CD-14-0477
10.1038/sj.cgt.7700775
10.18632/oncotarget.5631
10.1016/j.ejca.2012.05.009
10.1158/1078-0432.CCR-15-0588
10.1200/JCO.2013.54.4932
10.1016/j.ccell.2014.11.013
10.1158/1535-7163.MCT-09-0499
10.1093/annonc/mdv027
10.1016/j.yexcr.2015.05.015
10.1016/j.devcel.2007.03.020
10.3390/vaccines3030519
10.1038/nature08822
10.1158/1535-7163.MCT-09-0381
10.1158/1078-0432.CCR-11-2381
10.1158/1078-0432.CCR-10-2621
10.1038/onc.2012.538
10.3389/fphar.2013.00030
10.1186/s12885-016-2847-3
10.1016/j.jhep.2013.09.008
10.1210/en.2012-2165
10.1371/journal.pone.0051189
10.1007/s10637-011-9715-4
10.1200/jco.2016.34.4_suppl.tps481
10.3892/ijo.2016.3401
10.1200/jco.2005.23.16_suppl.3112
10.1158/2159-8290.CD-12-0446
10.1155/2012/804801
10.1186/s12885-015-1803-y
10.1038/srep31072
10.1002/ijc.28737
10.1158/1078-0432.CCR-14-0114
10.1158/1538-7445.am2015-ct237
10.1158/0008-5472.CAN-14-3358
10.1158/1535-7163.MCT-10-0318
10.18632/oncotarget.9837
10.1111/cas.12906
10.1200/JCO.2010.33.0670
10.1038/onc.2013.460
10.1016/j.ejca.2007.03.009
10.1093/annonc/mdv222
10.1200/jco.2013.31.15_suppl.5515
10.1158/1078-0432.CCR-10-3336
10.1093/jnci/djw182
10.1200/jco.2011.29.15_suppl.7584
10.1200/jco.2010.28.15_suppl.3026
10.1158/0008-5472.CAN-10-2274
10.1155/2015/538019
10.1126/scitranslmed.3010445
10.1002/gcc.10157
10.1158/1078-0432.CCR-14-0265
10.1097/JTO.0b013e31823c5b11
10.1200/JCO.2016.34.15_suppl.530
10.1158/1535-7163.MCT-12-0447
10.1158/0008-5472.CAN-10-0052
10.1158/0008-5472.CAN-16-1201
10.1038/35060032
10.1007/s10911-008-9104-6
10.4081/oncol.2013.e3
10.1158/0008-5472.sabcs-09-402
10.1016/j.bbrc.2010.12.038
10.18632/oncotarget.9100
10.1126/science.1235122
10.1189/jlb.0404248
10.1158/1078-0432.CCR-13-0145
10.1210/jc.2012-3856
10.1158/1535-7163.MCT-06-0080
10.1007/s10637-014-0177-3
10.1038/nm759
10.1530/ERC-13-0231
10.1186/s40169-015-0048-3
10.2337/db11-1776
10.1128/MCB.14.6.3604
10.1002/j.1460-2075.1986.tb04528.x
10.3389/fendo.2012.00021
10.1056/NEJMc1509660
10.1530/EJE-10-0859
10.1158/0008-5472.CAN-04-1837
10.1200/JCO.2009.23.6745
10.1056/NEJMoa1507643
10.1038/sj.onc.1210715
10.1158/1535-7163.MCT-13-0255
10.1038/364308a0
10.1016/S0140-6736(15)01281-7
10.1158/1078-0432.CCR-10-2979
10.18632/oncotarget.8484
10.1200/JCO.2013.54.8404
10.1158/0008-5472.CAN-12-2066
10.1007/s00280-009-1083-9
10.1242/dmm.015362
10.1038/nrc3720
10.1172/JCI34588
10.1007/s10637-014-0170-x
10.1056/NEJMoa1003466
10.1016/j.jhep.2014.11.011
10.1200/JCO.2014.59.0018
10.1158/1535-7163.MCT-14-0144
10.1371/journal.pone.0135844
10.1200/JCO.2009.24.6611
10.1158/1538-7445.AM2015-420
10.1002/mc.22342
10.2174/13816128113199990596
10.1158/1078-0432.CCR-07-1118
10.1016/S1535-6108(04)00051-0
10.1158/1535-7163.MCT-12-1067
10.1158/1078-0432.CCR-07-0648
10.1016/j.ctrv.2014.07.004
10.1158/1078-0432.CCR-13-2752
10.1677/erc.1.01280
10.1080/15384101.2016.1160982
10.1158/1078-0432.CCR-15-2218
10.1158/0008-5472.sabcs13-p2-16-04
10.4161/onci.20925
10.1038/nature11249
10.1002/ijc.24623
10.1186/1471-2407-13-170
10.1158/1535-7163.MCT-13-0598
10.1186/1476-4598-13-71
10.18632/oncotarget.8013
10.1038/onc.2015.229
10.1158/1535-7163.MCT-11-0205
10.1200/JCO.2010.34.0000
10.1002/pbc.26087
10.1016/S1470-2045(15)00083-2
10.1016/j.ejca.2013.06.010
10.4155/fmc.09.89
10.2174/1574362409666140206221931
10.1158/1078-0432.CCR-09-3220
10.1158/0008-5472.CAN-14-0970
10.1200/jco.2015.33.3_suppl.384
10.1126/scisignal.2004014
10.1021/jm9002395
10.1038/onc.2015.326
10.1038/370527a0
10.1158/1535-7163.MCT-16-0313
10.3389/fendo.2015.00077
10.3390/cancers2020233
10.1016/j.ccr.2010.10.031
10.1158/1078-0432.CCR-08-1401
10.1126/scitranslmed.3001845
10.3389/fendo.2015.00092
10.1172/JCI57909
10.1126/scisignal.2003184
10.1200/jco.2013.31.15_suppl.6030
10.1200/jco.2014.32.15_suppl.2622
10.1002/jcb.24080
10.1016/S1470-2045(13)70026-3
10.1158/0008-5472.CAN-06-1712
10.1093/annonc/mdr574
10.1016/S1470-2045(13)70019-6
10.1016/0092-8674(91)90557-F
10.18632/oncotarget.10862
10.1016/j.cell.2011.02.013
10.1007/s00280-014-2391-2
10.1158/1078-0432.CCR-09-2719
10.1038/378785a0
10.1007/BF02736791
10.1016/j.neo.2015.03.001
10.1016/S1470-2045(09)70354-7
10.18632/oncotarget.3425
10.1038/bjc.2014.497
10.1200/jco.2001.19.8.2189
10.1186/s12943-015-0392-3
ContentType Journal Article
Copyright The Author(s) 2017
Targeted Oncology is a copyright of Springer, 2017.
Copyright_xml – notice: The Author(s) 2017
– notice: Targeted Oncology is a copyright of Springer, 2017.
DBID C6C
AAYXX
CITATION
CGR
CUY
CVF
ECM
EIF
NPM
3V.
7RV
7X7
7XB
88E
8AO
8FI
8FJ
8FK
ABUWG
AFKRA
AZQEC
BENPR
CCPQU
FYUFA
GHDGH
K9-
K9.
KB0
M0R
M0S
M1P
NAPCQ
PHGZM
PHGZT
PJZUB
PKEHL
PPXIY
PQEST
PQQKQ
PQUKI
PRINS
7X8
5PM
DOI 10.1007/s11523-017-0514-5
DatabaseName Springer Nature Open Access Journals
CrossRef
Medline
MEDLINE
MEDLINE (Ovid)
MEDLINE
MEDLINE
PubMed
ProQuest Central (Corporate)
Nursing & Allied Health Database
ProQuest Health & Medical Collection
ProQuest Central (purchase pre-March 2016)
Medical Database (Alumni Edition)
ProQuest Pharma Collection
Hospital Premium Collection
Hospital Premium Collection (Alumni Edition)
ProQuest Central (Alumni) (purchase pre-March 2016)
ProQuest Central (Alumni)
ProQuest Central UK/Ireland
ProQuest Central Essentials
ProQuest Central (subscription)
ProQuest One
Health Research Premium Collection
Health Research Premium Collection (Alumni)
Consumer Health Database
ProQuest Health & Medical Complete (Alumni)
Nursing & Allied Health Database (Alumni Edition)
Consumer Health Database
ProQuest Health & Medical Collection
Medical Database
Nursing & Allied Health Premium
ProQuest Central Premium
ProQuest One Academic
ProQuest Health & Medical Research Collection
ProQuest One Academic Middle East (New)
ProQuest One Health & Nursing
ProQuest One Academic Eastern Edition (DO NOT USE)
ProQuest One Academic (retired)
ProQuest One Academic UKI Edition
ProQuest Central China
MEDLINE - Academic
PubMed Central (Full Participant titles)
DatabaseTitle CrossRef
MEDLINE
Medline Complete
MEDLINE with Full Text
PubMed
MEDLINE (Ovid)
ProQuest One Academic Middle East (New)
ProQuest Central Essentials
ProQuest Health & Medical Complete (Alumni)
ProQuest Central (Alumni Edition)
ProQuest One Community College
ProQuest One Health & Nursing
ProQuest Pharma Collection
ProQuest Family Health (Alumni Edition)
ProQuest Central China
ProQuest Central
ProQuest Health & Medical Research Collection
Health Research Premium Collection
Health and Medicine Complete (Alumni Edition)
Health & Medical Research Collection
ProQuest Central (New)
ProQuest Medical Library (Alumni)
ProQuest Family Health
ProQuest One Academic Eastern Edition
ProQuest Nursing & Allied Health Source
ProQuest Hospital Collection
Health Research Premium Collection (Alumni)
ProQuest Hospital Collection (Alumni)
Nursing & Allied Health Premium
ProQuest Health & Medical Complete
ProQuest Medical Library
ProQuest One Academic UKI Edition
ProQuest Nursing & Allied Health Source (Alumni)
ProQuest One Academic
ProQuest One Academic (New)
ProQuest Central (Alumni)
MEDLINE - Academic
DatabaseTitleList
ProQuest One Academic Middle East (New)
MEDLINE - Academic
MEDLINE
Database_xml – sequence: 1
  dbid: NPM
  name: PubMed
  url: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed
  sourceTypes: Index Database
– sequence: 2
  dbid: 7RV
  name: Nursing & Allied Health Database
  url: https://search.proquest.com/nahs
  sourceTypes: Aggregation Database
DeliveryMethod fulltext_linktorsrc
Discipline Medicine
EISSN 1776-260X
EndPage 597
ExternalDocumentID PMC5610669
28815409
10_1007_s11523_017_0514_5
Genre Research Support, Non-U.S. Gov't
Journal Article
Review
GrantInformation_xml – fundername: Boehringer Ingelheim
  funderid: http://dx.doi.org/10.13039/100008349
– fundername: Cancer Research UK
– fundername: ;
GroupedDBID ---
-5E
-5G
-BR
-EM
-Y2
-~C
.86
.VR
04C
06C
06D
0R~
0VY
123
1N0
29Q
2J2
2JN
2JY
2KG
2KM
2VQ
2~H
30V
3V.
4.4
406
408
409
40D
40E
53G
5VS
67Z
6NX
7RV
7X7
88E
8AO
8FI
8FJ
8TC
8UJ
95-
95.
95~
96X
AAAVM
AABHQ
AACDK
AAIAL
AAIKX
AAJKR
AANXM
AANZL
AARHV
AARTL
AASML
AATNV
AAWCG
AAYIU
AAYQN
AAYTO
AAYZH
ABAKF
ABBBX
ABBXA
ABDZT
ABFTV
ABHLI
ABJNI
ABJOX
ABKCH
ABKTR
ABMNI
ABNWP
ABPLI
ABQBU
ABQSL
ABTKH
ABTMW
ABUWG
ABXPI
ACAOD
ACCOQ
ACDTI
ACGFS
ACHVE
ACHXU
ACIHN
ACKNC
ACMJI
ACMLO
ACOKC
ACOMO
ACPIV
ACREN
ACSNA
ACZOJ
ADBBV
ADFZG
ADHHG
ADHIR
ADINQ
ADRFC
ADURQ
ADYOE
AEAQA
AEBTG
AEFQL
AEGAL
AEGNC
AEJHL
AEJRE
AEKMD
AEMSY
AENEX
AEOHA
AEPYU
AESKC
AETLH
AEVLU
AEXYK
AFALF
AFBBN
AFKRA
AFLOW
AFWTZ
AFYQB
AFZKB
AGAYW
AGDGC
AGJBK
AGQEE
AGQMX
AGRTI
AGWIL
AGWZB
AGYKE
AHAVH
AHBYD
AHMBA
AHSBF
AHYZX
AIAKS
AIGIU
AIIXL
AILAN
AJBLW
AJRNO
ALIPV
ALMA_UNASSIGNED_HOLDINGS
ALWAN
AMKLP
AMTXH
AMXSW
AMYLF
AMYQR
ANMIH
ARMRJ
ASPBG
AVWKF
AWSVR
AXYYD
AZFZN
AZQEC
B-.
BA0
BENPR
BGNMA
BKEYQ
BKNYI
BMSDO
BPHCQ
BVXVI
C6C
CAG
CCPQU
COF
CS3
DL5
DNIVK
DPUIP
DU5
EBD
EBLON
EBS
EIHBH
EIOEI
EJD
EMOBN
EN4
ESBYG
EX3
F5P
FEDTE
FERAY
FFXSO
FIGPU
FLLZZ
FNLPD
FRRFC
FSGXE
FWDCC
FYUFA
G-Y
G-Z
GGCAI
GGRSB
GJIRD
GNWQR
GQ6
GQ7
GQ8
GXS
H13
HF~
HG5
HG6
HLICF
HMCUK
HMJXF
HQYDN
HRMNR
HVGLF
HZ~
IHE
IJ-
ITM
IWAJR
IXC
IXE
IZIGR
IZQ
I~X
I~Z
J-C
JBSCW
JCJTX
JZLTJ
K9-
KDC
KOV
KPH
LGEZI
LLZTM
LOTEE
M0R
M1P
M4Y
MA-
N2Q
NADUK
NAPCQ
NQJWS
NU0
NXXTH
O9-
O93
O9I
OAM
P9S
PF0
PQQKQ
PROAC
PSQYO
QOR
QOS
R89
R9I
RIG
ROL
RPX
RSV
S16
S1Z
S27
S37
S3B
SAP
SDH
SHX
SJYHP
SMD
SNE
SNPRN
SNX
SOHCF
SOJ
SPKJE
SRMVM
SSLCW
SV3
SZ9
SZN
T13
TSG
TSK
TSV
TT1
TUC
U2A
U9L
UG4
UKHRP
UTJUX
UZXMN
VC2
VDBLX
VFIZW
W23
W48
WJK
WK8
WOW
Z45
Z7U
Z82
Z87
ZMTXR
~A9
~JE
AAYXX
ABBRH
ABDBE
ABFSG
ABRTQ
ACSTC
ADHKG
AEZWR
AFDZB
AFFHD
AFHIU
AFOHR
AGQPQ
AHWEU
AIXLP
ATHPR
AYFIA
CITATION
PHGZM
PHGZT
PJZUB
PPXIY
CGR
CUY
CVF
ECM
EIF
NPM
7XB
8FK
K9.
PKEHL
PQEST
PQUKI
PRINS
7X8
PUEGO
5PM
ID FETCH-LOGICAL-c536t-f83f59250631100b8b7a1f773dfe7e52a89cd34f17b06f7a57f2ec130391d4443
IEDL.DBID BENPR
ISICitedReferencesCount 132
ISICitedReferencesURI http://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestLinkType=CitingArticles&DestApp=WOS_CPL&KeyUT=000411741500002&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D
ISSN 1776-2596
1776-260X
IngestDate Tue Nov 04 01:48:42 EST 2025
Fri Sep 05 13:50:36 EDT 2025
Fri Nov 07 23:29:06 EST 2025
Mon Jul 21 06:05:42 EDT 2025
Sat Nov 29 03:34:08 EST 2025
Tue Nov 18 22:46:24 EST 2025
Fri Feb 21 02:31:55 EST 2025
IsDoiOpenAccess true
IsOpenAccess true
IsPeerReviewed true
IsScholarly true
Issue 5
Language English
License Open Access This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/), which permits any noncommercial use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
LinkModel DirectLink
MergedId FETCHMERGED-LOGICAL-c536t-f83f59250631100b8b7a1f773dfe7e52a89cd34f17b06f7a57f2ec130391d4443
Notes ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 14
ObjectType-Review-3
content type line 23
OpenAccessLink https://link.springer.com/10.1007/s11523-017-0514-5
PMID 28815409
PQID 1941897196
PQPubID 1486337
PageCount 27
ParticipantIDs pubmedcentral_primary_oai_pubmedcentral_nih_gov_5610669
proquest_miscellaneous_1930486056
proquest_journals_1941897196
pubmed_primary_28815409
crossref_citationtrail_10_1007_s11523_017_0514_5
crossref_primary_10_1007_s11523_017_0514_5
springer_journals_10_1007_s11523_017_0514_5
PublicationCentury 2000
PublicationDate 2017-10-01
PublicationDateYYYYMMDD 2017-10-01
PublicationDate_xml – month: 10
  year: 2017
  text: 2017-10-01
  day: 01
PublicationDecade 2010
PublicationPlace Cham
PublicationPlace_xml – name: Cham
– name: France
– name: Paris
PublicationTitle Targeted oncology
PublicationTitleAbbrev Targ Oncol
PublicationTitleAlternate Target Oncol
PublicationYear 2017
Publisher Springer International Publishing
Springer Nature B.V
Publisher_xml – name: Springer International Publishing
– name: Springer Nature B.V
References Van Cutsem E, Eng C, Nowara E, Swieboda-Sadlej A, Tebbutt NC, Mitchell E, et al. Randomized phase Ib/II trial of rilotumumab or ganitumab with panitumumab versus panitumumab alone in patients with wild-type KRAS metastatic colorectal cancer. Clin Cancer Res. 2014;20(16):4240–50. doi:10.1158/1078-0432.CCR-13-2752.
Chiappori AA, Otterson GA, Dowlati A, Traynor AM, Horn L, Owonikoko TK, et al. A randomized phase II study of Linsitinib (OSI-906) versus Topotecan in patients with relapsed small-cell lung cancer. Oncologist. 2016;21(10):1163–4. doi:10.1634/theoncologist.2016-0220.
Friedbichler K, Hofmann MH, Kroez M, Ostermann E, Lamche HR, Koessl C, et al. Pharmacodynamic and antineoplastic activity of BI 836845, a fully human IGF ligand-neutralizing antibody, and mechanistic rationale for combination with rapamycin. Mol Cancer Ther. 2014;13(2):399–409. doi:10.1158/1535-7163.MCT-13-0598.
Craddock BP, Miller WT. Effects of somatic mutations in the C-terminus of insulin-like growth factor 1 receptor on activity and signaling. J Signal Transduct. 2012;2012:804801. doi:10.1155/2012/804801.
Pappo AS, Patel SR, Crowley J, Reinke DK, Kuenkele KP, Chawla SP, et al. R1507, a monoclonal antibody to the insulin-like growth factor 1 receptor, in patients with recurrent or refractory Ewing sarcoma family of tumors: results of a phase II sarcoma alliance for research through collaboration study. J Clin Oncol. 2011;29(34):4541–7. doi:10.1200/JCO.2010.34.0000.
Zinn RL, Gardner EE, Marchionni L, Murphy SC, Dobromilskaya I, Hann CL, et al. ERK phosphorylation is predictive of resistance to IGF-1R inhibition in small cell lung cancer. Mol Cancer Ther. 2013;12(6):1131–9. doi:10.1158/1535-7163.MCT-12-0618.
Vidal SJ, Rodriguez-Bravo V, Quinn SA, Rodriguez-Barrueco R, Lujambio A, Williams E, et al. A targetable GATA2-IGF2 axis confers aggressiveness in lethal prostate cancer. Cancer Cell. 2015;27(2):223–39. doi:10.1016/j.ccell.2014.11.013.
Ferte C, Loriot Y, Clemenson C, Commo F, Gombos A, Bibault JE, et al. IGF-1R targeting increases the antitumor effects of DNA-damaging agents in SCLC model: an opportunity to increase the efficacy of standard therapy. Mol Cancer Ther. 2013;12(7):1213–22. doi:10.1158/1535-7163.MCT-12-1067.
Suda K, Mizuuchi H, Sato K, Takemoto T, Iwasaki T, Mitsudomi T. The insulin-like growth factor 1 receptor causes acquired resistance to erlotinib in lung cancer cells with the wild-type epidermal growth factor receptor. Int J Cancer. 2014;135(4):1002–6. doi:10.1002/ijc.28737.
Rochester MA, Riedemann J, Hellawell GO, Brewster SF, Macaulay VM. Silencing of the IGF1R gene enhances sensitivity to DNA-damaging agents in both PTEN wild-type and mutant human prostate cancer. Cancer Gene Ther. 2005;12(1):90–100. doi:10.1038/sj.cgt.7700775.
van de Luijtgaarden AC, Versleijen-Jonkers YM, Roeffen MH, Schreuder HW, Flucke UE, van der Graaf WT. Prognostic and therapeutic relevance of the IGF pathway in Ewing’s sarcoma patients. Target Oncol. 2013;8(4):253–60. doi:10.1007/s11523-012-0248-3.
Mulvihill MJ, Cooke A, Rosenfeld-Franklin M, Buck E, Foreman K, Landfair D, et al. Discovery of OSI-906: a selective and orally efficacious dual inhibitor of the IGF-1 receptor and insulin receptor. Future Med Chem. 2009;1(6):1153–71. doi:10.4155/fmc.09.89.
Becker MA, Hou X, Tienchaianada P, Haines BB, Harrington SC, Weroha SJ, et al. Ridaforolimus (MK-8669) synergizes with Dalotuzumab (MK-0646) in hormone-sensitive breast cancer. BMC Cancer. 2016;16(1):814. doi:10.1186/s12885-016-2847-3.
Werner H, Roberts CT Jr. The IGFI receptor gene: a molecular target for disrupted transcription factors. Genes Chromosom Cancer. 2003;36(2):113–20. doi:10.1002/gcc.10157.
Baselga J, Morales S, Awada A, Blum J, Tan A, Ewertz M, et al. A phase 2 study of ridaforolimus (RIDA) and dalotuzumab (DALO) in estrogen receptor positive (ER+) breast cancer. Cancer Res. 2013;73(24 suppl)abstr: P2-16-04. doi:10.1158/0008-5472.sabcs13-p2-16-04.
Min HY, Yun HJ, Lee JS, Lee HJ, Cho J, Jang HJ, et al. Targeting the insulin-like growth factor receptor and Src signaling network for the treatment of non-small cell lung cancer. Mol Cancer. 2015;14:113. doi:10.1186/s12943-015-0392-3.
Di Cosimo S, Seoane J, Guzman M, Rojo F, Jimenez J, Anido J et al. Combination of the mammalian target of rapamycin (mTOR) inhibitor everolimus (E) with the insulin like growth factor-1-receptor (IGF-1-R) inhibitor NVP-AEW-541: A mechanistic based anti-tumor strategy. J Clin Oncol. 2005;23(16 suppl):abstr 3112.
ResnicoffMSellCRubiniMCoppolaDAmbroseDBasergaRRat glioblastoma cells expressing an antisense RNA to the insulin-like growth factor-1 (IGF-1) receptor are nontumorigenic and induce regression of wild-type tumorsCancer Res1994548221822221:CAS:528:DyaK2cXis1ahsro%3D8174129
Deng H, Lin Y, Badin M, Vasilcanu D, Stromberg T, Jernberg-Wiklund H, et al. Over-accumulation of nuclear IGF-1 receptor in tumor cells requires elevated expression of the receptor and the SUMO-conjugating enzyme Ubc9. Biochem Biophys Res Commun. 2011;404(2):667–71. doi:10.1016/j.bbrc.2010.12.038.
Evdokimova V, Tognon CE, Benatar T, Yang W, Krutikov K, Pollak M, et al. IGFBP7 binds to the IGF-1 receptor and blocks its activation by insulin-like growth factors. Sci Signal. 2012;5(255):ra92. doi:10.1126/scisignal.2003184.
Somasundaram R, Zhang G, Wagner SN, Fukunaga-Kalabis M, Herlyn M. The role of tumor microenvironment in therapy resistance and melanoma progression. Cancer Res. 2015;75 (15 suppl):abstr 420.
Zha J, O’Brien C, Savage H, Huw LY, Zhong F, Berry L, et al. Molecular predictors of response to a humanized anti-insulin-like growth factor-I receptor monoclonal antibody in breast and colorectal cancer. Mol Cancer Ther. 2009;8(8):2110–21. doi:10.1158/1535-7163.MCT-09-0381.
Olmos D, Postel-Vinay S, Molife LR, Okuno SH, Schuetze SM, Paccagnella ML, et al. Safety, pharmacokinetics, and preliminary activity of the anti-IGF-1R antibody figitumumab (CP-751,871) in patients with sarcoma and Ewing’s sarcoma: a phase 1 expansion cohort study. Lancet Oncol. 2010;11(2):129–35. doi:10.1016/S1470-2045(09)70354-7.
Malaguarnera R, Belfiore A. The emerging role of insulin and insulin-like growth factor signaling in cancer stem cells. Front Endocrinol (Lausanne). 2014;5:10. doi:10.3389/fendo.2014.00010.
Shin I, Yakes FM, Rojo F, Shin NY, Bakin AV, Baselga J, et al. PKB/Akt mediates cell-cycle progression by phosphorylation of p27(Kip1) at threonine 157 and modulation of its cellular localization. Nat Med. 2002;8(10):1145–52. doi:10.1038/nm759.
Bignell GR, Greenman CD, Davies H, Butler AP, Edkins S, Andrews JM, et al. Signatures of mutation and selection in the cancer genome. Nature. 2010;463(7283):893–8. doi:10.1038/nature08768.
Chitnis MM, Yuen JS, Protheroe AS, Pollak M, Macaulay VM. The type 1 insulin-like growth factor receptor pathway. Clin Cancer Res. 2008;14(20):6364–70. doi:10.1158/1078-0432.CCR-07-4879.
Borghaei H, Paz-Ares L, Horn L, Spigel DR, Steins M, Ready NE, et al. Nivolumab versus docetaxel in advanced Nonsquamous non-small-cell lung cancer. N Engl J Med. 2015;373(17):1627–39. doi:10.1056/NEJMoa1507643.
Anguela XM, Tafuro S, Roca C, Callejas D, Agudo J, Obach M, et al. Nonviral-mediated hepatic expression of IGF-I increases Treg levels and suppresses autoimmune diabetes in mice. Diabetes. 2013;62(2):551–60. doi:10.2337/db11-1776.
Turney BW, Kerr M, Chitnis MM, Lodhia K, Wang Y, Riedemann J, et al. Depletion of the type 1 IGF receptor delays repair of radiation-induced DNA double strand breaks. Radiother Oncol. 2012;103(3):402–9. doi:10.1016/j.radonc.2012.03.009.
Wilson S, Chia SK. IGF-1R inhibition: right direction, wrong pathway? Lancet Oncol. 2013;14(3):182–3. doi:10.1016/S1470-2045(13)70019-6.
Heerboth S, Housman G, Leary M, Longacre M, Byler S, Lapinska K, et al. EMT and tumor metastasis. Clin Transl Med. 2015;4:6. doi:10.1186/s40169-015-0048-3.
Bilbao D, Luciani L, Johannesson B, Piszczek A, Rosenthal N. Insulin-like growth factor-1 stimulates regulatory T cells and suppresses autoimmune disease. EMBO Mol Med. 2014;6(11):1423–35. doi:10.15252/emmm.201303376.
Beltran PJ, Mitchell P, Chung YA, Cajulis E, Lu J, Belmontes B, et al. AMG 479, a fully human anti-insulin-like growth factor receptor type I monoclonal antibody, inhibits the growth and survival of pancreatic carcinoma cells. Mol Cancer Ther. 2009;8(5):1095–1105. doi:10.1158/1535-7163.MCT-08-1171.
Pavlicek A, Lira ME, Lee NV, Ching KA, Ye J, Cao J, et al. Molecular predictors of sensitivity to the insulin-like growth factor 1 receptor inhibitor Figitumumab (CP-751,871). Mol Cancer Ther. 2013;12(12):2929–39. doi:10.1158/1535-7163.MCT-13-0442-T.
Molina-Arcas M, Hancock DC, Sheridan C, Kumar MS, Downward J. Coordinate direct input of both KRAS and IGF1 receptor to activation of PI3 kinase in KRAS-mutant lung cancer. Cancer Discov. 2013;3(5):548–63. doi:10.1158/2159-8290.CD-12-0446.
Steuerman R, Shevah O, Laron Z. Congenital IGF1 deficiency tends to confer protection against post-natal development of malignancies. Eur J Endocrinol. 2011;164(4):485–9. doi:10.1530/EJE-10-0859.
Simone BA, Dan T, Palagani A, Jin L, Han SY, Wright C, et al. Caloric restriction coupled with radiation decreases metastatic burden in triple negative breast cancer. Cell Cycle. 2016;15(17):2265–74. doi:10.1080/15384101.2016.1160982.
Calvo E, Ma W, Tolcher AW, Hidalgo M, Soria J, Bahleda R et al. Phase (P) I study of PF-00299804 (PF) combined with figitumumab (FI; CP-751871) in patients (pts) with advanced solid tumors (ASTs). J Clin Oncol. 2010;28(15 suppl): abstr 3026.
Langer CJ, Novello S, Park K, Krzakowski M, Karp DD, Mok T, et al. Randomized, phase III trial of first-line figitumumab in combination with paclitaxel and carboplatin versus paclitaxel and carboplatin alone in patients with advanced non-small-cell lung cancer. J Clin Oncol. 2014;32(19):2059–66. doi:10.1200/JCO.2013.54.4932.
Rota LM, Wood TL. Crosstalk of the insulin-like growth factor receptor with the Wnt signaling pathway in breast cancer. Front Endocrinol (Lausanne).
514_CR203
514_CR202
514_CR201
514_CR200
514_CR33
514_CR34
514_CR31
514_CR32
514_CR30
514_CR39
514_CR38
514_CR44
514_CR45
514_CR42
514_CR43
514_CR40
514_CR41
514_CR48
514_CR46
514_CR47
514_CR11
514_CR7
514_CR12
514_CR8
K Ohtani (514_CR37) 1995; 92
514_CR9
514_CR10
514_CR17
514_CR18
514_CR15
514_CR14
M Resnicoff (514_CR212) 1994; 54
514_CR22
514_CR23
514_CR21
514_CR28
514_CR29
514_CR26
514_CR27
514_CR24
514_CR25
C Liu (514_CR49) 2014; 20
514_CR199
514_CR198
514_CR197
514_CR196
T Doi (514_CR79) 2016; 27
F Matsumoto (514_CR142) 2012; 32
514_CR191
514_CR190
514_CR195
514_CR194
514_CR193
514_CR192
A Ullrich (514_CR6) 1986; 5
J Kato (514_CR36) 1993; 7
514_CR188
514_CR187
H Werner (514_CR16) 1996; 7
514_CR186
514_CR185
S Burrow (514_CR19) 1998; 69
514_CR189
514_CR180
514_CR184
514_CR183
514_CR182
514_CR181
514_CR177
514_CR176
514_CR175
514_CR174
514_CR179
514_CR178
514_CR173
514_CR172
514_CR171
514_CR170
514_CR166
514_CR165
514_CR164
514_CR163
514_CR169
514_CR168
514_CR167
514_CR162
514_CR161
514_CR160
514_CR155
514_CR154
K Habben (514_CR125) 2011; 29
514_CR153
514_CR152
514_CR159
514_CR158
514_CR157
514_CR156
514_CR151
514_CR150
514_CR149
514_CR144
514_CR143
514_CR141
514_CR148
514_CR147
514_CR146
CC Lin (514_CR78) 2014; 32
514_CR91
514_CR92
514_CR90
514_CR140
514_CR99
514_CR97
514_CR98
514_CR95
514_CR96
514_CR139
514_CR138
C Sell (514_CR13) 1994; 14
J Trojan (514_CR213) 1993; 259
C Garcia-Echeverria (514_CR64) 2004; 5
514_CR133
514_CR132
514_CR131
514_CR130
514_CR137
514_CR136
514_CR135
514_CR134
J Desai (514_CR94) 2010; 28
514_CR129
514_CR128
514_CR127
SP Chellappan (514_CR35) 1991; 65
514_CR122
514_CR120
514_CR126
A Chakravarti (514_CR145) 2002; 62
514_CR124
514_CR123
514_CR70
514_CR77
514_CR75
514_CR76
514_CR73
514_CR74
514_CR71
514_CR72
514_CR119
514_CR118
514_CR117
514_CR116
514_CR111
514_CR110
514_CR115
514_CR114
514_CR113
I Ray-Coquard (514_CR93) 2013; 31
514_CR112
514_CR80
514_CR81
514_CR1
514_CR2
514_CR3
514_CR4
514_CR5
514_CR88
514_CR89
514_CR86
514_CR87
514_CR84
514_CR85
514_CR82
514_CR83
MA Steller (514_CR20) 1996; 56
514_CR108
514_CR107
514_CR106
514_CR105
514_CR109
514_CR100
514_CR221
514_CR220
514_CR104
514_CR103
514_CR102
514_CR101
MM Jalve (514_CR121) 2012; 30
514_CR222
514_CR55
514_CR56
514_CR53
514_CR54
514_CR51
514_CR52
514_CR50
514_CR218
514_CR217
514_CR216
514_CR215
514_CR59
514_CR57
514_CR58
514_CR219
514_CR210
514_CR214
514_CR211
514_CR66
514_CR67
514_CR65
514_CR62
514_CR63
514_CR60
514_CR61
514_CR207
514_CR206
514_CR205
514_CR204
514_CR68
514_CR209
514_CR69
514_CR208
References_xml – reference: Vidal SJ, Rodriguez-Bravo V, Quinn SA, Rodriguez-Barrueco R, Lujambio A, Williams E, et al. A targetable GATA2-IGF2 axis confers aggressiveness in lethal prostate cancer. Cancer Cell. 2015;27(2):223–39. doi:10.1016/j.ccell.2014.11.013.
– reference: Chitnis MM, Yuen JS, Protheroe AS, Pollak M, Macaulay VM. The type 1 insulin-like growth factor receptor pathway. Clin Cancer Res. 2008;14(20):6364–70. doi:10.1158/1078-0432.CCR-07-4879.
– reference: Ramcharan R, Aleksic T, Kamdoum WP, Gao S, Pfister SX, Tanner J, et al. IGF-1R inhibition induces schedule-dependent sensitization of human melanoma to temozolomide. Oncotarget. 2015;6(37):39877–90. doi:10.18632/oncotarget.5631.
– reference: Zeng X, Sachdev D, Zhang H, Gaillard-Kelly M, Yee D. Sequencing of type I insulin-like growth factor receptor inhibition affects chemotherapy response in vitro and in vivo. Clin Cancer Res. 2009;15(8):2840–9. doi:10.1158/1078-0432.CCR-08-1401.
– reference: Parker C, Gillessen S, Heidenreich A, Horwich A. Cancer of the prostate: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2015;26(suppl 5):v69–77. doi:10.1093/annonc/mdv222.
– reference: Hoyo C, Schildkraut JM, Murphy SK, Chow WH, Vaughan TL, Risch H, et al. IGF2R polymorphisms and risk of esophageal and gastric adenocarcinomas. Int J Cancer. 2009;125(11):2673–8. doi:10.1002/ijc.24623.
– reference: Zinn RL, Gardner EE, Marchionni L, Murphy SC, Dobromilskaya I, Hann CL, et al. ERK phosphorylation is predictive of resistance to IGF-1R inhibition in small cell lung cancer. Mol Cancer Ther. 2013;12(6):1131–9. doi:10.1158/1535-7163.MCT-12-0618.
– reference: ChellappanSPHiebertSMudryjMHorowitzJMNevinsJRThe E2F transcription factor is a cellular target for the RB proteinCell1991656105310611:CAS:528:DyaK3MXks12nsrg%3D10.1016/0092-8674(91)90557-F1828392
– reference: Arcaro A. Targeting the insulin-like growth factor-1 receptor in human cancer. Front Pharmacol. 2013;4:30. doi:10.3389/fphar.2013.00030.
– reference: Jin M, Buck E, Mulvihill MJ. Modulation of insulin-like growth factor-1 receptor and its signaling network for the treatment of cancer: current status and future perspectives. Oncol Rev. 2013;7(1):e3. doi:10.4081/oncol.2013.e3.
– reference: DesaiJSolomonBJDavisIDLiptonLRHicksRScottAMPhase I dose-escalation study of daily BMS-754807, an oral, dual IGF-1R/insulin receptor (IR) inhibitor in subjects with solid tumorsJ Clin Oncol201028suppl 15abstr 310410.1200/jco.2010.28.15_suppl.3104
– reference: Sachdev D, Yee D. Disrupting insulin-like growth factor signaling as a potential cancer therapy. Mol Cancer Ther. 2007;6(1):1–12. doi:10.1158/1535-7163.MCT-06-0080.
– reference: DoiTShitaraKNaitoYKubokiYKojimaTHosonoAPhase I dose escalation trial of weekly intravenous xentuzumab (BI 836845) in Japanese patients with advanced solid tumorsAnn Oncol201627supplabstr 2790
– reference: Lin MZ, Marzec KA, Martin JL, Baxter RC. The role of insulin-like growth factor binding protein-3 in the breast cancer cell response to DNA-damaging agents. Oncogene. 2014;33(1):85–96. doi:10.1038/onc.2012.538.
– reference: Werner H, Roberts CT Jr. The IGFI receptor gene: a molecular target for disrupted transcription factors. Genes Chromosom Cancer. 2003;36(2):113–20. doi:10.1002/gcc.10157.
– reference: Kurzrock R, Patnaik A, Aisner J, Warren T, Leong S, Benjamin R, et al. A phase I study of weekly R1507, a human monoclonal antibody insulin-like growth factor-I receptor antagonist, in patients with advanced solid tumors. Clin Cancer Res. 2010;16(8):2458–65. doi:10.1158/1078-0432.CCR-09-3220.
– reference: Bignell GR, Greenman CD, Davies H, Butler AP, Edkins S, Andrews JM, et al. Signatures of mutation and selection in the cancer genome. Nature. 2010;463(7283):893–8. doi:10.1038/nature08768.
– reference: Haluska P, Worden F, Olmos D, Yin D, Schteingart D, Batzel GN, et al. Safety, tolerability, and pharmacokinetics of the anti-IGF-1R monoclonal antibody figitumumab in patients with refractory adrenocortical carcinoma. Cancer Chemother Pharmacol. 2010;65(4):765–73. doi:10.1007/s00280-009-1083-9.
– reference: Han J, Zhao F, Zhang J, Zhu H, Ma H, Li X, et al. miR-223 reverses the resistance of EGFR-TKIs through IGF1R/PI3K/Akt signaling pathway. Int J Oncol. 2016;48(5):1855–67. doi:10.3892/ijo.2016.3401.
– reference: Deng H, Lin Y, Badin M, Vasilcanu D, Stromberg T, Jernberg-Wiklund H, et al. Over-accumulation of nuclear IGF-1 receptor in tumor cells requires elevated expression of the receptor and the SUMO-conjugating enzyme Ubc9. Biochem Biophys Res Commun. 2011;404(2):667–71. doi:10.1016/j.bbrc.2010.12.038.
– reference: Chandarlapaty S, Sawai A, Scaltriti M, Rodrik-Outmezguine V, Grbovic-Huezo O, Serra V, et al. AKT inhibition relieves feedback suppression of receptor tyrosine kinase expression and activity. Cancer Cell. 2011;19(1):58–71. doi:10.1016/j.ccr.2010.10.031.
– reference: De Meyts P, Palsgaard J, Sajid W, Theede AM, Aladdin H. Structural biology of insulin and IGF-1 receptors. Novartis Found Symp. 2004;262:160–71. discussion 71-6, 265-8.
– reference: Asmane I, Watkin E, Alberti L, Duc A, Marec-Berard P, Ray-Coquard I, et al. Insulin-like growth factor type 1 receptor (IGF-1R) exclusive nuclear staining: a predictive biomarker for IGF-1R monoclonal antibody (ab) therapy in sarcomas. Eur J Cancer. 2012;48(16):3027–35. doi:10.1016/j.ejca.2012.05.009.
– reference: Di Cosimo S, Seoane J, Guzman M, Rojo F, Jimenez J, Anido J et al. Combination of the mammalian target of rapamycin (mTOR) inhibitor everolimus (E) with the insulin like growth factor-1-receptor (IGF-1-R) inhibitor NVP-AEW-541: A mechanistic based anti-tumor strategy. J Clin Oncol. 2005;23(16 suppl):abstr 3112.
– reference: Andrews DW, Resnicoff M, Flanders AE, Kenyon L, Curtis M, Merli G, et al. Results of a pilot study involving the use of an antisense oligodeoxynucleotide directed against the insulin-like growth factor type I receptor in malignant astrocytomas. J Clin Oncol. 2001;19(8):2189–200. doi:10.1200/jco.2001.19.8.2189.
– reference: Flanigan SA, Pitts TM, Newton TP, Kulikowski GN, Tan AC, McManus MC, et al. Overcoming IGF1R/IR resistance through inhibition of MEK signaling in colorectal cancer models. Clin Cancer Res. 2013;19(22):6219–29. doi:10.1158/1078-0432.CCR-13-0145.
– reference: Pappo AS, Vassal G, Crowley JJ, Bolejack V, Hogendoorn PC, Chugh R, et al. A phase 2 trial of R1507, a monoclonal antibody to the insulin-like growth factor-1 receptor (IGF-1R), in patients with recurrent or refractory rhabdomyosarcoma, osteosarcoma, synovial sarcoma, and other soft tissue sarcomas: results of a sarcoma alliance for research through collaboration study. Cancer. 2014;120(16):2448–56. doi:10.1002/cncr.28728.
– reference: Pappo AS, Patel SR, Crowley J, Reinke DK, Kuenkele KP, Chawla SP, et al. R1507, a monoclonal antibody to the insulin-like growth factor 1 receptor, in patients with recurrent or refractory Ewing sarcoma family of tumors: results of a phase II sarcoma alliance for research through collaboration study. J Clin Oncol. 2011;29(34):4541–7. doi:10.1200/JCO.2010.34.0000.
– reference: Johannesson B, Sattler S, Semenova E, Pastore S, Kennedy-Lydon TM, Sampson RD, et al. Insulin-like growth factor-1 induces regulatory T cell-mediated suppression of allergic contact dermatitis in mice. Dis Model Mech. 2014;7(8):977–85. doi:10.1242/dmm.015362.
– reference: Mancarella C, Casanova-Salas I, Calatrava A, Ventura S, Garofalo C, Rubio-Briones J, et al. ERG deregulation induces IGF-1R expression in prostate cancer cells and affects sensitivity to anti-IGF-1R agents. Oncotarget. 2015;6(18):16611–22. doi:10.18632/oncotarget.3425.
– reference: Cortot AB, Repellin CE, Shimamura T, Capelletti M, Zejnullahu K, Ercan D, et al. Resistance to irreversible EGF receptor tyrosine kinase inhibitors through a multistep mechanism involving the IGF1R pathway. Cancer Res. 2013;73(2):834–43. doi:10.1158/0008-5472.CAN-12-2066.
– reference: Bowers LW, Rossi EL, O’Flanagan CH, de Graffenried LA, Hursting SD. The role of the insulin/IGF system in cancer: lessons learned from clinical trials and the energy balance-cancer link. Front Endocrinol (Lausanne). 2015;6:77. doi:10.3389/fendo.2015.00077.
– reference: Leighl NB, Rizvi NA, de Lima LG Jr, Arpornwirat W, Rudin CM, Chiappori AA, et al. Phase 2 study of Erlotinib in combination with Linsitinib (OSI-906) or placebo in chemotherapy-naive patients with non-small-cell lung cancer and activating epidermal growth factor receptor mutations. Clin Lung Cancer. 2017;18(1):34–42.e2. doi:10.1016/j.cllc.2016.07.007.
– reference: Zhang XF, Settleman J, Kyriakis JM, Takeuchi-Suzuki E, Elledge SJ, Marshall MS, et al. Normal and oncogenic p21ras proteins bind to the amino-terminal regulatory domain of c-Raf-1. Nature. 1993;364(6435):308–13. doi:10.1038/364308a0.
– reference: Pavlicek A, Lira ME, Lee NV, Ching KA, Ye J, Cao J, et al. Molecular predictors of sensitivity to the insulin-like growth factor 1 receptor inhibitor Figitumumab (CP-751,871). Mol Cancer Ther. 2013;12(12):2929–39. doi:10.1158/1535-7163.MCT-13-0442-T.
– reference: Brahmkhatri VP, Prasanna C, Atreya HS. Insulin-like growth factor system in cancer: novel targeted therapies. Biomed Res Int. 2015;2015:538019. doi:10.1155/2015/538019.
– reference: Borghaei H, Paz-Ares L, Horn L, Spigel DR, Steins M, Ready NE, et al. Nivolumab versus docetaxel in advanced Nonsquamous non-small-cell lung cancer. N Engl J Med. 2015;373(17):1627–39. doi:10.1056/NEJMoa1507643.
– reference: Olmos D, Postel-Vinay S, Molife LR, Okuno SH, Schuetze SM, Paccagnella ML, et al. Safety, pharmacokinetics, and preliminary activity of the anti-IGF-1R antibody figitumumab (CP-751,871) in patients with sarcoma and Ewing’s sarcoma: a phase 1 expansion cohort study. Lancet Oncol. 2010;11(2):129–35. doi:10.1016/S1470-2045(09)70354-7.
– reference: Denduluri SK, Idowu O, Wang Z, Liao Z, Yan Z, Mohammed MK, et al. Insulin-like growth factor (IGF) signaling in tumorigenesis and the development of cancer drug resistance. Genes Dis. 2015;2(1):13–25. doi:10.1016/j.gendis.2014.10.004.
– reference: Rota LM, Wood TL. Crosstalk of the insulin-like growth factor receptor with the Wnt signaling pathway in breast cancer. Front Endocrinol (Lausanne). 2015;6:92. doi:10.3389/fendo.2015.00092.
– reference: von Manstein V, Yang CM, Richter D, Delis N, Vafaizadeh V, Groner B. Resistance of cancer cells to targeted therapies through the activation of compensating signaling loops. Curr Signal Transduct Ther. 2013;8(3):193–202. doi:10.2174/1574362409666140206221931.
– reference: JalveMMShroffRTVaradhacharyGRWolffRAFogelmanDRBhosalePTumor IGF-1 expression as a predictive biomarker for IGF1R-directed therapy in advanced pancreatic cancer (APC)J Clin Oncol201230supplabstr 4054
– reference: Park K, Cho KH, Lee KH, Su W, Kim S, Lin C et al. Phase Ib trial of afatinib and xentuzumab (BI 836845) in advanced NSCLC: dose-escalation and safety results. J Thorac Oncol. 2017;12(1, suppl):S1187–S1188.
– reference: Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646–74. doi:10.1016/j.cell.2011.02.013.
– reference: Ribas A, Puzanov I, Dummer R, Schadendorf D, Hamid O, Robert C, et al. Pembrolizumab versus investigator-choice chemotherapy for ipilimumab-refractory melanoma (KEYNOTE-002): a randomised, controlled, phase 2 trial. Lancet Oncol. 2015;16(8):908–18. doi:10.1016/S1470-2045(15)00083-2.
– reference: MatsumotoFValdecanasDNMasonKAMilasLAngKKRajuUThe impact of timing of EGFR and IGF-1R inhibition for sensitizing head and neck cancer to radiationAnticancer Res2012328302930351:CAS:528:DC%2BC38Xht1KmurbM22843870
– reference: Calvo E, Ma W, Tolcher AW, Hidalgo M, Soria J, Bahleda R et al. Phase (P) I study of PF-00299804 (PF) combined with figitumumab (FI; CP-751871) in patients (pts) with advanced solid tumors (ASTs). J Clin Oncol. 2010;28(15 suppl): abstr 3026.
– reference: Baxter RC. IGF binding proteins in cancer: mechanistic and clinical insights. Nat Rev Cancer. 2014;14(5):329–41. doi:10.1038/nrc3720.
– reference: Zha J, O’Brien C, Savage H, Huw LY, Zhong F, Berry L, et al. Molecular predictors of response to a humanized anti-insulin-like growth factor-I receptor monoclonal antibody in breast and colorectal cancer. Mol Cancer Ther. 2009;8(8):2110–21. doi:10.1158/1535-7163.MCT-09-0381.
– reference: Bendell JC, Jones SF, Hart L, Spigel DR, Lane CM, Earwood C, et al. A phase Ib study of linsitinib (OSI-906), a dual inhibitor of IGF-1R and IR tyrosine kinase, in combination with everolimus as treatment for patients with refractory metastatic colorectal cancer. Investig New Drugs. 2015;33(1):187–93. doi:10.1007/s10637-014-0177-3.
– reference: Cross DA, Alessi DR, Cohen P, Andjelkovich M, Hemmings BA. Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B. Nature. 1995;378(6559):785–9. doi:10.1038/378785a0.
– reference: Larkin J, Hodi FS, Wolchok JD. Combined Nivolumab and Ipilimumab or monotherapy in untreated melanoma. N Engl J Med. 2015;373(13):1270–1. doi:10.1056/NEJMc1509660.
– reference: Cortes J, Martinez Janez N, Sablin MP, Perez-Fidalgo JA, Neven P, Hedayati E et al. Phase 1b/2 trial of BI 836845, an insulin-like growth factor (IGF) ligand-neutralizing antibody, combined with exemestane (Ex) and everolimus (Ev) in hormone receptor-positive (HR+) locally advanced or metastatic breast cancer (BC): primary phase 1b results. J Clin Oncol. 2016;34(suppl):abstr 530.
– reference: Sciacca L, Le MR, Vigneri R. Insulin analogs and cancer. Front Endocrinol (Lausanne). 2012;3:21. doi:10.3389/fendo.2012.00021.
– reference: Abou-Alfa GK, Capanu M, O’Reilly EM, Ma J, Chou JF, Gansukh B, et al. A phase II study of cixutumumab (IMC-A12, NSC742460) in advanced hepatocellular carcinoma. J Hepatol. 2014;60(2):319–24. doi:10.1016/j.jhep.2013.09.008.
– reference: Van Cutsem E, Eng C, Nowara E, Swieboda-Sadlej A, Tebbutt NC, Mitchell E, et al. Randomized phase Ib/II trial of rilotumumab or ganitumab with panitumumab versus panitumumab alone in patients with wild-type KRAS metastatic colorectal cancer. Clin Cancer Res. 2014;20(16):4240–50. doi:10.1158/1078-0432.CCR-13-2752.
– reference: Girnita L, Worrall C, Takahashi S, Seregard S, Girnita A. Something old, something new and something borrowed: emerging paradigm of insulin-like growth factor type 1 receptor (IGF-1R) signaling regulation. Cell Mol Life Sci. 2014;71(13):2403–27. doi:10.1007/s00018-013-1514-y.
– reference: Pollak M. The insulin and insulin-like growth factor receptor family in neoplasia: an update. Nat Rev Cancer. 2012;12(3):159–69. doi:10.1038/nrc3215.
– reference: Shimizu T, Tolcher AW, Papadopoulos KP, Beeram M, Rasco DW, Smith LS, et al. The clinical effect of the dual-targeting strategy involving PI3K/AKT/mTOR and RAS/MEK/ERK pathways in patients with advanced cancer. Clin Cancer Res. 2012;18(8):2316–25. doi:10.1158/1078-0432.CCR-11-2381.
– reference: Browne BC, Crown J, Venkatesan N, Duffy MJ, Clynes M, Slamon D, et al. Inhibition of IGF1R activity enhances response to trastuzumab in HER-2-positive breast cancer cells. Ann Oncol. 2011;22(1):68–73. doi:10.1093/annonc/mdq349.
– reference: Herkert B, Kauffmann A, Molle S, Schnell C, Ferrat T, Voshol H, et al. Maximizing the efficacy of MAPK-targeted treatment in PTENLOF/BRAFMUT melanoma through PI3K and IGF1R inhibition. Cancer Res. 2016;76(2):390–402. doi:10.1158/0008-5472.CAN-14-3358.
– reference: USA Department of Health and Human Services Food and Drug Administration. Guidance for Industry: Adaptive Design Clinical Trials for Drugs and Biologics. 2010. http://www.fda.gov/downloads/Drugs/.../Guidances/ucm201790.pdf
– reference: Fuchs CS, Azevedo S, Okusaka T, Van Laethem JL, Lipton LR, Riess H, et al. A phase 3 randomized, double-blind, placebo-controlled trial of ganitumab or placebo in combination with gemcitabine as first-line therapy for metastatic adenocarcinoma of the pancreas: the GAMMA trial. Ann Oncol. 2015;26(5):921–7. doi:10.1093/annonc/mdv027.
– reference: Malaguarnera R, Belfiore A. The emerging role of insulin and insulin-like growth factor signaling in cancer stem cells. Front Endocrinol (Lausanne). 2014;5:10. doi:10.3389/fendo.2014.00010.
– reference: Garcia-EcheverriaCPearsonMAMartiAMeyerTMestanJZimmermannJIn vivo antitumor activity of NVP-AEW541-a novel, potent, and selective inhibitor of the IGF-IR kinaseCancer Cell2004532312391:CAS:528:DC%2BD2cXjtVartbk%3D10.1016/S1535-6108(04)00051-015050915
– reference: Cao H, Dong W, Qu X, Shen H, Xu J, Zhu L, et al. Metformin enhances the therapy effects of Anti-IGF-1R mAb Figitumumab to NSCLC. Sci Rep. 2016;6:31072. doi:10.1038/srep31072.
– reference: Atzori F, Tabernero J, Cervantes A, Prudkin L, Andreu J, Rodriguez-Braun E, et al. A phase I pharmacokinetic and pharmacodynamic study of dalotuzumab (MK-0646), an anti-insulin-like growth factor-1 receptor monoclonal antibody, in patients with advanced solid tumors. Clin Cancer Res. 2011;17(19):6304–12. doi:10.1158/1078-0432.CCR-10-3336.
– reference: Wilson S, Chia SK. IGF-1R inhibition: right direction, wrong pathway? Lancet Oncol. 2013;14(3):182–3. doi:10.1016/S1470-2045(13)70019-6.
– reference: Rodriguez-Viciana P, Warne PH, Dhand R, Vanhaesebroeck B, Gout I, Fry MJ, et al. Phosphatidylinositol-3-OH kinase as a direct target of Ras. Nature. 1994;370(6490):527–32. doi:10.1038/370527a0.
– reference: Miller ML, Molinelli EJ, Nair JS, Sheikh T, Samy R, Jing X, et al. Drug synergy screen and network modeling in dedifferentiated liposarcoma identifies CDK4 and IGF1R as synergistic drug targets. Sci Signal. 2013;6(294):ra85. doi:10.1126/scisignal.2004014.
– reference: Bielen A, Perryman L, Box GM, Valenti M, de Haven BA, Martins V, et al. Enhanced efficacy of IGF1R inhibition in pediatric glioblastoma by combinatorial targeting of PDGFRalpha/beta. Mol Cancer Ther. 2011;10(8):1407–18. doi:10.1158/1535-7163.MCT-11-0205.
– reference: Simone BA, Dan T, Palagani A, Jin L, Han SY, Wright C, et al. Caloric restriction coupled with radiation decreases metastatic burden in triple negative breast cancer. Cell Cycle. 2016;15(17):2265–74. doi:10.1080/15384101.2016.1160982.
– reference: Pandini G, Mineo R, Frasca F, Roberts CT Jr, Marcelli M, Vigneri R, et al. Androgens up-regulate the insulin-like growth factor-I receptor in prostate cancer cells. Cancer Res. 2005;65(5):1849–57. doi:10.1158/0008-5472.CAN-04-1837.
– reference: Dasari A, Phan A, Gupta S, Rashid A, Yeung SC, Hess K, et al. Phase I study of the anti-IGF1R antibody cixutumumab with everolimus and octreotide in advanced well-differentiated neuroendocrine tumors. Endocr Relat Cancer. 2015;22(3):431–41. doi:10.1530/ERC-15-0002.
– reference: Fitzgerald JB, Johnson BW, Baum J, Adams S, Iadevaia S, Tang J, et al. MM-141, an IGF-IR- and ErbB3-directed bispecific antibody, overcomes network adaptations that limit activity of IGF-IR inhibitors. Mol Cancer Ther. 2014;13(2):410–25. doi:10.1158/1535-7163.MCT-13-0255.
– reference: Yamaoka T, Ohmori T, Ohba M, Arata S, Kishino Y, Murata Y, et al. Acquired resistance mechanisms to combination met-TKI/EGFR-TKI exposure in met-amplified EGFR-TKI resistant lung adenocarcinoma harboring an activating EGFR mutation. Mol Cancer Ther. 2016;15(12):3040–54. doi:10.1158/1535-7163.MCT-16-0313.
– reference: Barrett JP, Minogue AM, Falvey A, Lynch MA. Involvement of IGF-1 and Akt in M1/M2 activation state in bone marrow-derived macrophages. Exp Cell Res. 2015;335(2):258–68. doi:10.1016/j.yexcr.2015.05.015.
– reference: Garon EB, Rizvi NA, Hui R, Leighl N, Balmanoukian AS, Eder JP, et al. Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med. 2015;372(21):2018–28. doi:10.1056/NEJMoa1501824.
– reference: King H, Aleksic T, Haluska P, Macaulay VM. Can we unlock the potential of IGF-1R inhibition in cancer therapy? Cancer Treat Rev. 2014;40(9):1096–105. doi:10.1016/j.ctrv.2014.07.004.
– reference: Turney BW, Kerr M, Chitnis MM, Lodhia K, Wang Y, Riedemann J, et al. Depletion of the type 1 IGF receptor delays repair of radiation-induced DNA double strand breaks. Radiother Oncol. 2012;103(3):402–9. doi:10.1016/j.radonc.2012.03.009.
– reference: Plymate SR, Haugk K, Coleman I, Woodke L, Vessella R, Nelson P, et al. An antibody targeting the type I insulin-like growth factor receptor enhances the castration-induced response in androgen-dependent prostate cancer. Clin Cancer Res. 2007;13(21):6429–39. doi:10.1158/1078-0432.CCR-07-0648.
– reference: Guix M, Faber AC, Wang SE, Olivares MG, Song Y, Qu S, et al. Acquired resistance to EGFR tyrosine kinase inhibitors in cancer cells is mediated by loss of IGF-binding proteins. J Clin Invest. 2008;118(7):2609–19. doi:10.1172/JCI34588.
– reference: Ebi H, Corcoran RB, Singh A, Chen Z, Song Y, Lifshits E, et al. Receptor tyrosine kinases exert dominant control over PI3K signaling in human KRAS mutant colorectal cancers. J Clin Invest. 2011;121(11):4311–21. doi:10.1172/JCI57909.
– reference: Sun S, Sprenger CC, Vessella RL, Haugk K, Soriano K, Mostaghel EA, et al. Castration resistance in human prostate cancer is conferred by a frequently occurring androgen receptor splice variant. J Clin Invest. 2010;120(8):2715–30. doi:10.1172/JCI41824.
– reference: Weroha SJ, Haluska P. IGF-1 receptor inhibitors in clinical trials--early lessons. J Mammary Gland Biol Neoplasia. 2008;13(4):471–83. doi:10.1007/s10911-008-9104-6.
– reference: Flashner-Abramson E, Klein S, Mullin G, Shoshan E, Song R, Shir A, et al. Targeting melanoma with NT157 by blocking Stat3 and IGF1R signaling. Oncogene. 2016;35(20):2675–80. doi:10.1038/onc.2015.229.
– reference: Bilbao D, Luciani L, Johannesson B, Piszczek A, Rosenthal N. Insulin-like growth factor-1 stimulates regulatory T cells and suppresses autoimmune disease. EMBO Mol Med. 2014;6(11):1423–35. doi:10.15252/emmm.201303376.
– reference: Gao J, Chesebrough JW, Cartlidge SA, Ricketts SA, Incognito L, Veldman-Jones M, et al. Dual IGF-I/II-neutralizing antibody MEDI-573 potently inhibits IGF signaling and tumor growth. Cancer Res. 2011;71(3):1029–40. doi:10.1158/0008-5472.CAN-10-2274.
– reference: Tolcher AW, Sarantopoulos J, Patnaik A, Papadopoulos K, Lin CC, Rodon J, et al. Phase I, pharmacokinetic, and pharmacodynamic study of AMG 479, a fully human monoclonal antibody to insulin-like growth factor receptor 1. J Clin Oncol. 2009;27(34):5800–7. doi:10.1200/JCO.2009.23.6745.
– reference: Sehat B, Tofigh A, Lin Y, Trocme E, Liljedahl U, Lagergren J, et al. SUMOylation mediates the nuclear translocation and signaling of the IGF-1 receptor. Sci Signal. 2010;3(108):ra10. doi:10.1126/scisignal.2000628.
– reference: Aleksic T, Chitnis MM, Perestenko OV, Gao S, Thomas PH, Turner GD, et al. Type 1 insulin-like growth factor receptor translocates to the nucleus of human tumor cells. Cancer Res. 2010;70(16):6412–9. doi:10.1158/0008-5472.CAN-10-0052.
– reference: Di Cosimo S, Sathyanarayanan S, Bendell JC, Cervantes A, Stein MN, Brana I, et al. Combination of the mTOR inhibitor ridaforolimus and the anti-IGF1R monoclonal antibody dalotuzumab: preclinical characterization and phase I clinical trial. Clin Cancer Res. 2015;21(1):49–59. doi:10.1158/1078-0432.CCR-14-0940.
– reference: Becerra CR, Salazar R, Garcia-Carbonero R, Thomas AL, Vazquez-Mazon FJ, Cassidy J, et al. Figitumumab in patients with refractory metastatic colorectal cancer previously treated with standard therapies: a nonrandomized, open-label, phase II trial. Cancer Chemother Pharmacol. 2014;73(4):695–702. doi:10.1007/s00280-014-2391-2.
– reference: Dziadziuszko R, Merrick DT, Witta SE, Mendoza AD, Szostakiewicz B, Szymanowska A, et al. Insulin-like growth factor receptor 1 (IGF1R) gene copy number is associated with survival in operable non-small-cell lung cancer: a comparison between IGF1R fluorescent in situ hybridization, protein expression, and mRNA expression. J Clin Oncol. 2010;28(13):2174–80. doi:10.1200/JCO.2009.24.6611.
– reference: Quek R, Wang Q, Morgan JA, Shapiro GI, Butrynski JE, Ramaiya N, et al. Combination mTOR and IGF-1R inhibition: phase I trial of everolimus and figitumumab in patients with advanced sarcomas and other solid tumors. Clin Cancer Res. 2011;17(4):871–9. doi:10.1158/1078-0432.CCR-10-2621.
– reference: Chiappori AA, Otterson GA, Dowlati A, Traynor AM, Horn L, Owonikoko TK, et al. A randomized phase II study of Linsitinib (OSI-906) versus Topotecan in patients with relapsed small-cell lung cancer. Oncologist. 2016;21(10):1163–4. doi:10.1634/theoncologist.2016-0220.
– reference: Lugovskoy AA, Curley M, Baum J, Adams S, Iadevaia S, Rimkunas V, et al. Preclinical characterization and first-in-human study of MM-141, a dual antibody inhibitor of IGF-1R and ErbB3. Cancer Res. 2015;75(15 suppl): abstr CT237-CT. doi:10.1158/1538-7445.am2015-ct237.
– reference: Wargo JA, Cooper ZA, Flaherty KT. Universes collide: combining immunotherapy with targeted therapy for cancer. Cancer Discov. 2014;4(12):1377–86. doi:10.1158/2159-8290.CD-14-0477.
– reference: Haluska P, Menefee M, Plimack ER, Rosenberg J, Northfelt D, LaVallee T, et al. Phase I dose-escalation study of MEDI-573, a bispecific, antiligand monoclonal antibody against IGFI and IGFII, in patients with advanced solid tumors. Clin Cancer Res. 2014;20(18):4747–57. doi:10.1158/1078-0432.CCR-14-0114.
– reference: Guevara-Aguirre J, Balasubramanian P, Guevara-Aguirre M, Wei M, Madia F, Cheng CW, et al. Growth hormone receptor deficiency is associated with a major reduction in pro-aging signaling, cancer, and diabetes in humans. Sci Transl Med. 2011;3(70):70ra13. doi:10.1126/scitranslmed.3001845.
– reference: Ioannou N, Seddon AM, Dalgleish A, Mackintosh D, Modjtahedi H. Treatment with a combination of the ErbB (HER) family blocker afatinib and the IGF-IR inhibitor, NVP-AEW541 induces synergistic growth inhibition of human pancreatic cancer cells. BMC Cancer. 2013;13(1):1–12. doi:10.1186/1471-2407-13-41.
– reference: O’Flanagan CH, O’Shea S, Lyons A, Fogarty FM, McCabe N, Kennedy RD, et al. IGF-1R inhibition sensitizes breast cancer cells to ATM-related kinase (ATR) inhibitor and cisplatin. Oncotarget. 2016;7(35):56826–56841. doi:10.18632/oncotarget.10862.
– reference: Brana I, Berger R, Golan T, Haluska P, Edenfield J, Fiorica J, et al. A parallel-arm phase I trial of the humanised anti-IGF-1R antibody dalotuzumab in combination with the AKT inhibitor MK-2206, the mTOR inhibitor ridaforolimus, or the NOTCH inhibitor MK-0752, in patients with advanced solid tumours. Br J Cancer. 2014;111(10):1932–44. doi:10.1038/bjc.2014.497.
– reference: Herbst RS, Baas P, Kim DW, Felip E, Perez-Gracia JL, Han JY, et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet. 2016;387(10027):1540–50. doi:10.1016/S0140-6736(15)01281-7.
– reference: Iguchi H, Nishina T, Nogami N, Kozuki T, Yamagiwa Y, Yagawa K. Phase I dose-escalation study evaluating safety, tolerability and pharmacokinetics of MEDI-573, a dual IGF-I/II neutralizing antibody, in Japanese patients with advanced solid tumours. Investig New Drugs. 2015;33(1):194–200. doi:10.1007/s10637-014-0170-x.
– reference: Hodi FS, O’Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363(8):711–23. doi:10.1056/NEJMoa1003466.
– reference: Molina-Arcas M, Hancock DC, Sheridan C, Kumar MS, Downward J. Coordinate direct input of both KRAS and IGF1 receptor to activation of PI3 kinase in KRAS-mutant lung cancer. Cancer Discov. 2013;3(5):548–63. doi:10.1158/2159-8290.CD-12-0446.
– reference: Chitnis MM, Lodhia KA, Aleksic T, Gao S, Protheroe AS, Macaulay VM. IGF-1R inhibition enhances radiosensitivity and delays double-strand break repair by both non-homologous end-joining and homologous recombination. Oncogene. 2014;33(45):5262–73. doi:10.1038/onc.2013.460.
– reference: Lee Y, Wang Y, James M, Jeong JH, You M. Inhibition of IGF1R signaling abrogates resistance to afatinib (BIBW2992) in EGFR T790M mutant lung cancer cells. Mol Carcinog. 2016;55(5):991–1001. doi:10.1002/mc.22342.
– reference: Carboni JM, Wittman M, Yang Z, Lee F, Greer A, Hurlburt W, et al. BMS-754807, a small molecule inhibitor of insulin-like growth factor-1R/IR. Mol Cancer Ther. 2009;8(12):3341–9. doi:10.1158/1535-7163.MCT-09-0499.
– reference: Shin I, Yakes FM, Rojo F, Shin NY, Bakin AV, Baselga J, et al. PKB/Akt mediates cell-cycle progression by phosphorylation of p27(Kip1) at threonine 157 and modulation of its cellular localization. Nat Med. 2002;8(10):1145–52. doi:10.1038/nm759.
– reference: Schmitz S, Kaminsky-Forrett MC, Henry S, Zanetta S, Geoffrois L, Bompas E, et al. Phase II study of figitumumab in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck: clinical activity and molecular response (GORTEC 2008-02). Ann Oncol. 2012;23(8):2153–61. doi:10.1093/annonc/mdr574.
– reference: Rihawi K, Ong M, Michalarea V, Bent L, Buschke S, Bogenrieder T et al. Phase I dose escalation study of 3-weekly BI 836845, a fully human, affinity optimized, insulin-like growth factor (IGF) ligand neutralizing antibody, in patients with advanced solid tumors. J Clin Oncol. 2014;32(5 suppl):abstr 2622.
– reference: Davaadelger B, Duan L, Perez RE, Gitelis S, Maki CG. Crosstalk between the IGF-1R/AKT/mTORC1 pathway and the tumor suppressors p53 and p27 determines cisplatin sensitivity and limits the effectiveness of an IGF-1R pathway inhibitor. Oncotarget. 2016;7(19):27511–26. doi:10.18632/oncotarget.8484.
– reference: Wilson TR, Fridlyand J, Yan Y, Penuel E, Burton L, Chan E, et al. Widespread potential for growth-factor-driven resistance to anticancer kinase inhibitors. Nature. 2012;487(7408):505–9. doi:10.1038/nature11249.
– reference: ResnicoffMSellCRubiniMCoppolaDAmbroseDBasergaRRat glioblastoma cells expressing an antisense RNA to the insulin-like growth factor-1 (IGF-1) receptor are nontumorigenic and induce regression of wild-type tumorsCancer Res1994548221822221:CAS:528:DyaK2cXis1ahsro%3D8174129
– reference: Basch E, Loblaw DA, Oliver TK, Carducci M, Chen RC, Frame JN, et al. Systemic therapy in men with metastatic castration-resistant prostate cancer: American Society of Clinical Oncology and Cancer Care Ontario clinical practice guideline. J Clin Oncol. 2014;32(30):3436–48. doi:10.1200/JCO.2013.54.8404.
– reference: Ferte C, Loriot Y, Clemenson C, Commo F, Gombos A, Bibault JE, et al. IGF-1R targeting increases the antitumor effects of DNA-damaging agents in SCLC model: an opportunity to increase the efficacy of standard therapy. Mol Cancer Ther. 2013;12(7):1213–22. doi:10.1158/1535-7163.MCT-12-1067.
– reference: Schwartz GK, Dickson MA, LoRusso PM, Sausville EA, Maekawa Y, Watanabe Y, et al. Preclinical and first-in-human phase I studies of KW-2450, an oral tyrosine kinase inhibitor with insulin-like growth factor receptor-1/insulin receptor selectivity. Cancer Sci. 2016;107(4):499–506. doi:10.1111/cas.12906.
– reference: Sprinzl MF, Puschnik A, Schlitter AM, Schad A, Ackermann K, Esposito I, et al. Sorafenib inhibits macrophage-induced growth of hepatoma cells by interference with insulin-like growth factor-1 secretion. J Hepatol. 2015;62(4):863–70. doi:10.1016/j.jhep.2014.11.011.
– reference: Haluska P, Shaw HM, Batzel GN, Yin D, Molina JR, Molife LR, et al. Phase I dose escalation study of the anti insulin-like growth factor-I receptor monoclonal antibody CP-751,871 in patients with refractory solid tumors. Clin Cancer Res. 2007;13(19):5834–40. doi:10.1158/1078-0432.CCR-07-1118.
– reference: OhtaniKDeGregoriJNevinsJRRegulation of the cyclin E gene by transcription factor E2F1Proc Natl Acad Sci U S A1995922612146121501:CAS:528:DyaK28Xhtl2itA%3D%3D10.1073/pnas.92.26.12146861886140313
– reference: Shen K, Cui D, Sun L, Lu Y, Han M, Liu J. Inhibition of IGF-IR increases chemosensitivity in human colorectal cancer cells through MRP-2 promoter suppression. J Cell Biochem. 2012;113(6):2086–97. doi:10.1002/jcb.24080.
– reference: Ko AH, Murray J, Horgan KE, Dauer J, Curley M, Baum J et al. A multicenter phase II study of istiratumab (MM-141) plus nab-paclitaxel (A) and gemcitabine (G) in metastatic pancreatic cancer (MPC). J Clin Oncol. 2016;34(4S suppl): abstr TPS481.
– reference: StellerMADelgadoCHBartelsCJWoodworthCDZouZOverexpression of the insulin-like growth factor-1 receptor and autocrine stimulation in human cervical cancer cellsCancer Res1996568176117651:CAS:528:DyaK28Xitlyksrs%3D8620490
– reference: Lu MC, Yu CL, Chen HC, Yu HC, Huang HB, Lai NS. Increased miR-223 expression in T cells from patients with rheumatoid arthritis leads to decreased insulin-like growth factor-1-mediated interleukin-10 production. Clin Exp Immunol. 2014;177(3):641–51. doi:10.1111/cei.12374.
– reference: Becker MA, Hou X, Tienchaianada P, Haines BB, Harrington SC, Weroha SJ, et al. Ridaforolimus (MK-8669) synergizes with Dalotuzumab (MK-0646) in hormone-sensitive breast cancer. BMC Cancer. 2016;16(1):814. doi:10.1186/s12885-016-2847-3.
– reference: Awasthi N, Zhang C, Ruan W, Schwarz MA, Schwarz RE. BMS-754807, a small-molecule inhibitor of insulin-like growth factor-1 receptor/insulin receptor, enhances gemcitabine response in pancreatic cancer. Mol Cancer Ther. 2012;11(12):2644–53. doi:10.1158/1535-7163.MCT-12-0447.
– reference: Rota LM, Albanito L, Shin ME, Goyeneche CL, Shushanov S, Gallagher EJ, et al. IGF1R inhibition in mammary epithelia promotes canonical Wnt signaling and Wnt1-driven tumors. Cancer Res. 2014;74(19):5668–79. doi:10.1158/0008-5472.CAN-14-0970.
– reference: Cardillo TM, Trisal P, Arrojo R, Goldenberg DM, Chang CH. Targeting both IGF-1R and mTOR synergistically inhibits growth of renal cell carcinoma in vitro. BMC Cancer. 2013;13:170. doi:10.1186/1471-2407-13-170.
– reference: Juergens H, Daw NC, Geoerger B, Ferrari S, Villarroel M, Aerts I, et al. Preliminary efficacy of the anti-insulin-like growth factor type 1 receptor antibody figitumumab in patients with refractory Ewing sarcoma. J Clin Oncol. 2011;29(34):4534–40. doi:10.1200/JCO.2010.33.0670.
– reference: Dean JP, Sprenger CC, Wan J, Haugk K, Ellis WJ, Lin DW, et al. Response of the insulin-like growth factor (IGF) system to IGF-IR inhibition and androgen deprivation in a neoadjuvant prostate cancer trial: effects of obesity and androgen deprivation. J Clin Endocrinol Metab. 2013;98(5):E820–8. doi:10.1210/jc.2012-3856.
– reference: McCaffery I, Tudor Y, Deng H, Tang R, Suzuki S, Badola S, et al. Putative predictive biomarkers of survival in patients with metastatic pancreatic adenocarcinoma treated with gemcitabine and ganitumab, an IGF1R inhibitor. Clin Cancer Res. 2013;19(15):4282–9. doi:10.1158/1078-0432.CCR-12-1840.
– reference: Beltran PJ, Mitchell P, Chung YA, Cajulis E, Lu J, Belmontes B, et al. AMG 479, a fully human anti-insulin-like growth factor receptor type I monoclonal antibody, inhibits the growth and survival of pancreatic carcinoma cells. Mol Cancer Ther. 2009;8(5):1095–1105. doi:10.1158/1535-7163.MCT-08-1171.
– reference: Zhang M, Hu Z, Huang J, Shu Y, Dai J, Jin G, et al. A 3′-untranslated region polymorphism in IGF1 predicts survival of non-small cell lung cancer in a Chinese population. Clin Cancer Res. 2010;16(4):1236–44. doi:10.1158/1078-0432.CCR-09-2719.
– reference: KatoJMatsushimeHHiebertSWEwenMESherrCJDirect binding of cyclin D to the retinoblastoma gene product (pRb) and pRb phosphorylation by the cyclin D-dependent kinase CDK4Genes Dev1993733313421:CAS:528:DyaK3sXltFertL4%3D10.1101/gad.7.3.3318449399
– reference: HabbenKDelmarPBrownsteinCMKoehlerWKuenkeleKSplesisOInvestigation of predictive biomarkers for R1507, an anti-IGF1R antibody, in patients with advanced non-small cell lung cancer with progression after first-line chemotherapyJ Clin Oncol201129supplabstr 758410.1200/jco.2011.29.15_suppl.7584
– reference: Tap WD, Demetri G, Barnette P, Desai J, Kavan P, Tozer R, et al. Phase II study of ganitumab, a fully human anti-type-1 insulin-like growth factor receptor antibody, in patients with metastatic Ewing family tumors or desmoplastic small round cell tumors. J Clin Oncol. 2012;30(15):1849–56. doi:10.1200/JCO.2011.37.2359.
– reference: Wang Y, Hailey J, Williams D, Wang Y, Lipari P, Malkowski M, et al. Inhibition of insulin-like growth factor-I receptor (IGF-IR) signaling and tumor cell growth by a fully human neutralizing anti-IGF-IR antibody. Mol Cancer Ther. 2005;4(8):1214–21. doi:10.1158/1535-7163.MCT-05-0048.
– reference: Osuka S, Sampetrean O, Shimizu T, Saga I, Onishi N, Sugihara E, et al. IGF1 receptor signaling regulates adaptive radioprotection in glioma stem cells. Stem Cells. 2013;31(4):627–40. doi:10.1002/stem.1328.
– reference: Oh SY, Shin A, Kim SG, Hwang JA, Hong SH, Lee YS, et al. Relationship between insulin-like growth factor axis gene polymorphisms and clinical outcome in advanced gastric cancer patients treated with FOLFOX. Oncotarget. 2016;7(21):31204–14. doi:10.18632/oncotarget.9100.
– reference: Pollak M. Insulin, insulin-like growth factors and neoplasia. Best Pract Res Clin Endocrinol Metab. 2008;22(4):625–38. doi:10.1016/j.beem.2008.08.004.
– reference: Kooijman R, Coppens A. Insulin-like growth factor-I stimulates IL-10 production in human T cells. J Leukoc Biol. 2004;76(4):862–7.
– reference: Langer CJ, Novello S, Park K, Krzakowski M, Karp DD, Mok T, et al. Randomized, phase III trial of first-line figitumumab in combination with paclitaxel and carboplatin versus paclitaxel and carboplatin alone in patients with advanced non-small-cell lung cancer. J Clin Oncol. 2014;32(19):2059–66. doi:10.1200/JCO.2013.54.4932.
– reference: Pandini G, Wurch T, Akla B, Corvaia N, Belfiore A, Goetsch L. Functional responses and in vivo anti-tumour activity of h7C10: a humanised monoclonal antibody with neutralising activity against the insulin-like growth factor-1 (IGF-1) receptor and insulin/IGF-1 hybrid receptors. Eur J Cancer. 2007;43(8):1318–27. doi:10.1016/j.ejca.2007.03.009.
– reference: Livingstone C. IGF2 and cancer. Endocr Relat Cancer. 2013;20(6):R321–39. doi:10.1530/ERC-13-0231.
– reference: LinCCChangKYHuangDCMarriottVBeijsterveldtLVChenLTA phase I dose escalation study of weekly BI 836845, a fully human, affinity-optimized, insulin-like growth factor (IGF) ligand neutralizing antibody, in patients with advanced solid cancersJ Clin Oncol2014325 supplabstr 2617
– reference: Ray-CoquardIHaluskaPO’ReillySCottuPHElitLProvencherDMA multicenter open-label phase II study of the efficacy and safety of ganitumab (AMG 479), a fully human monoclonal antibody against insulin-like growth factor type 1 receptor (IGF-1R) as second-line therapy in patients with recurrent platinum-sensitive ovarian cancerJ Clin Oncol201331supplabstr 5515
– reference: Jones RL, Kim ES, Nava-Parada P, Alam S, Johnson FM, Stephens AW, et al. Phase I study of intermittent oral dosing of the insulin-like growth factor-1 and insulin receptors inhibitor OSI-906 in patients with advanced solid tumors. Clin Cancer Res. 2015;21(4):693–700. doi:10.1158/1078-0432.CCR-14-0265.
– reference: ChakravartiALoefflerJSDysonNJInsulin-like growth factor receptor I mediates resistance to anti-epidermal growth factor receptor therapy in primary human glioblastoma cells through continued activation of phosphoinositide 3-kinase signalingCancer Res20026212002071:CAS:528:DC%2BD38XntV2hsA%3D%3D11782378
– reference: Overholser J, Ambegaokar KH, Eze SM, Sanabria-Figueroa E, Nahta R, Bekaii-Saab T, et al. Anti-tumor effects of peptide therapeutic and peptide vaccine antibody co-targeting HER-1 and HER-2 in esophageal cancer (EC) and HER-1 and IGF-1R in triple-negative breast cancer (TNBC). Vaccines (Basel). 2015;3(3):519–43. doi:10.3390/vaccines3030519.
– reference: Wan X, Yeung C, Heske C, Mendoza A, Helman LJ. IGF-1R inhibition activates a YES/SFK bypass resistance pathway: rational basis for co-targeting IGF-1R and yes/SFK kinase in rhabdomyosarcoma. Neoplasia. 2015;17(4):358–66. doi:10.1016/j.neo.2015.03.001.
– reference: Anguela XM, Tafuro S, Roca C, Callejas D, Agudo J, Obach M, et al. Nonviral-mediated hepatic expression of IGF-I increases Treg levels and suppresses autoimmune diabetes in mice. Diabetes. 2013;62(2):551–60. doi:10.2337/db11-1776.
– reference: Park JH, Choi YJ, Kim SY, Lee JE, Sung KJ, Park S, et al. Activation of the IGF1R pathway potentially mediates acquired resistance to mutant-selective 3rd-generation EGF receptor tyrosine kinase inhibitors in advanced non-small cell lung cancer. Oncotarget. 2016;7(16):22005–15. doi:10.18632/oncotarget.8013.
– reference: Ma Y, Tang N, Thompson RC, Mobley BC, Clark SW, Sarkaria JN, et al. InsR/IGF1R pathway mediates resistance to EGFR inhibitors in glioblastoma. Clin Cancer Res. 2016;22(7):1767–76. doi:10.1158/1078-0432.CCR-15-1677.
– reference: Li R, Pourpak A, Morris SW. Inhibition of the insulin-like growth factor-1 receptor (IGF1R) tyrosine kinase as a novel cancer therapy approach. J Med Chem. 2009;52(16):4981–5004. doi:10.1021/jm9002395.
– reference: Glisson BS, Tseng J, Marur S, Shin DM, Murphy BA, Cohen EEW et al. Randomized phase II trial of cixutumumab (CIX) alone or with cetuximab (CET) for refractory recurrent/metastatic squamous cancer of head and neck (R/M-SCCHN). J Clin Oncol. 2013;31(suppl):abstr 6030.
– reference: Zhong H, Fazenbaker C, Chen C, Breen S, Huang J, Yao X, et al. Overproduction of IGF-2 drives a subset of colorectal cancer cells, which specifically respond to an anti-IGF therapeutic antibody and combination therapies. Oncogene. 2017;36(6):797–806. doi:10.1038/onc.2016.248.
– reference: Corcoran C, Rani S, Breslin S, Gogarty M, Ghobrial IM, Crown J, et al. miR-630 targets IGF1R to regulate response to HER-targeting drugs and overall cancer cell progression in HER2 over-expressing breast cancer. Mol Cancer. 2014;13:71. doi:10.1186/1476-4598-13-71.
– reference: van de Luijtgaarden AC, Versleijen-Jonkers YM, Roeffen MH, Schreuder HW, Flucke UE, van der Graaf WT. Prognostic and therapeutic relevance of the IGF pathway in Ewing’s sarcoma patients. Target Oncol. 2013;8(4):253–60. doi:10.1007/s11523-012-0248-3.
– reference: Amin O, Beauchamp MC, Nader PA, Laskov I, Iqbal S, Philip CA, et al. Suppression of homologous recombination by insulin-like growth factor-1 inhibition sensitizes cancer cells to PARP inhibitors. BMC Cancer. 2015;15:817. doi:10.1186/s12885-015-1803-y.
– reference: Goto Y, Sekine I, Tanioka M, Shibata T, Tanai C, Asahina H, et al. Figitumumab combined with carboplatin and paclitaxel in treatment-naive Japanese patients with advanced non-small cell lung cancer. Investig New Drugs. 2012;30(4):1548–56. doi:10.1007/s10637-011-9715-4.
– reference: Craddock BP, Miller WT. Effects of somatic mutations in the C-terminus of insulin-like growth factor 1 receptor on activity and signaling. J Signal Transduct. 2012;2012:804801. doi:10.1155/2012/804801.
– reference: Haluska P, Hou X, Huang F, Harrington S, Greer A, Macedo L, et al. Complete IGF signaling blockade by the dual-kinase inhibitor, BMS-754807, is sufficient to overcome tamoxifen and Letrozole resistance in vitro and in vivo. Cancer Res. 2009;69(24 suppl):402. doi:10.1158/0008-5472.sabcs-09-402.
– reference: Robertson JF, Ferrero JM, Bourgeois H, Kennecke H, de Boer RH, Jacot W, et al. Ganitumab with either exemestane or fulvestrant for postmenopausal women with advanced, hormone-receptor-positive breast cancer: a randomised, controlled, double-blind, phase 2 trial. Lancet Oncol. 2013;14(3):228–35. doi:10.1016/S1470-2045(13)70026-3.
– reference: Sclafani F, Kim TY, Cunningham D, Kim TW, Tabernero J, Schmoll HJ, et al. A randomized phase II/III study of Dalotuzumab in combination with Cetuximab and irinotecan in Chemorefractory, KRAS wild-type, metastatic colorectal cancer. J Natl Cancer Inst. 2015;107(12):djv258. doi:10.1093/jnci/djv258.
– reference: Averous J, Fonseca BD, Proud CG. Regulation of cyclin D1 expression by mTORC1 signaling requires eukaryotic initiation factor 4E-binding protein 1. Oncogene. 2008;14(27(8)):1106–13. doi: 10.1038/sj.onc.1210715.
– reference: UllrichAGrayATamAWYang-FengTTsubokawaMCollinsCInsulin-like growth factor I receptor primary structure: comparison with insulin receptor suggests structural determinants that define functional specificityEMBO J1986510250325121:CAS:528:DyaL2sXhtl2isw%3D%3D28778711167146
– reference: Martinez-Quetglas I, Pinyol R, Dauch D, Torrecilla S, Tovar V, Moeini A, et al. IGF2 is upregulated by epigenetic mechanisms in hepatocellular carcinomas and is an actionable oncogene product in experimental models. Gastroenterology. 2016;151(6):1192–1205 doi:10.1053/j.gastro.2016.09.001.
– reference: Feng Y, Dimitrov DS. Antibody-based therapeutics against components of the IGF system. Oncoimmunology. 2012;1(8):1390–1. doi:10.4161/onci.20925.
– reference: Zhong H, Fazenbaker C, Breen S, Chen C, Huang J, Morehouse C, et al. MEDI-573, alone or in combination with mammalian target of rapamycin inhibitors, targets the insulin-like growth factor pathway in sarcomas. Mol Cancer Ther. 2014;13(11):2662–73. doi:10.1158/1535-7163.MCT-14-0144.
– reference: Baserga R. The decline and fall of the IGF-I receptor. J Cell Physiol. 2013;228(4):675–9. doi:10.1002/jcp.24217.
– reference: Vogelstein B, Papadopoulos N, Velculescu VE, Zhou S, Diaz LA Jr, Kinzler KW. Cancer genome landscapes. Science. 2013;339(6127):1546–58. doi:10.1126/science.1235122.
– reference: Gradishar WJ, Yardley DA, Layman R, Sparano JA, Chuang E, Northfelt DW, et al. Clinical and translational results of a phase II, randomized trial of an Anti-IGF-1R (Cixutumumab) in women with breast cancer that progressed on endocrine therapy. Clin Cancer Res. 2016;22(2):301–9. doi:10.1158/1078-0432.CCR-15-0588.
– reference: Maris C, D’Haene N, Trepant AL, Le MM, Sauvage S, Allard J, et al. IGF-IR: a new prognostic biomarker for human glioblastoma. Br J Cancer. 2015;113(5):729–37. doi:10.1038/bjc.2015.242.
– reference: LiuCZhangZTangHJiangZYouLLiaoYCrosstalk between IGF-1R and other tumor promoting pathwaysCurr Pharm Des20142017291229211:CAS:528:DC%2BC2cXpt1Whurk%3D10.2174/1381612811319999059623944361
– reference: Quail DF, Bowman RL, Akkari L, Quick ML, Schuhmacher AJ, Huse JT, et al. The tumor microenvironment underlies acquired resistance to CSF-1R inhibition in gliomas. Science. 2016;352(6288) doi:10.1126/science.aad3018.
– reference: Sarfstein R, Werner H. Minireview: nuclear insulin and insulin-like growth factor-1 receptors: a novel paradigm in signal transduction. Endocrinology. 2013;154(5):1672–9. doi:10.1210/en.2012-2165.
– reference: Heilmann AM, Perera RM, Ecker V, Nicolay BN, Bardeesy N, Benes CH, et al. CDK4/6 and IGF1 receptor inhibitors synergize to suppress the growth of p16INK4A-deficient pancreatic cancers. Cancer Res. 2014;74(14):3947–58. doi:10.1158/0008-5472.CAN-13-2923.
– reference: Zhou BP, Liao Y, Xia W, Spohn B, Lee MH, Hung MC. Cytoplasmic localization of p21Cip1/WAF1 by Akt-induced phosphorylation in HER-2/neu-overexpressing cells. Nat Cell Biol. 2001;3(3):245–52. doi:10.1038/35060032.
– reference: Sarfstein R, Belfiore A, Werner H. Identification of insulin-like growth factor-I receptor (IGF-IR) Gene promoter-binding proteins in estrogen receptor (ER)-positive and ER-depleted breast cancer cells. Cancers (Basel). 2010;2(2):233–61. doi:10.3390/cancers2020233.
– reference: Macaulay VM, Middleton MR, Eckhardt SG, Rudin CM, Juergens RA, Gedrich R, et al. Phase I dose-escalation study of Linsitinib (OSI-906) and Erlotinib in patients with advanced solid tumors. Clin Cancer Res. 2016;22(12):2897-907. doi:10.1158/1078-0432.CCR-15-2218.
– reference: Chan JY, LaPara K, Yee D. Disruption of insulin receptor function inhibits proliferation in endocrine-resistant breast cancer cells. Oncogene. 2016;35(32):4235–43. doi:10.1038/onc.2015.488.
– reference: Isakoff SJ, Saleh MN, Lugovskoy AA, Mathews S, Czibere AG, Shields AF et al. First-in-human study of MM-141: a novel tetravalent monoclonal antibody targeting IGF-1R and ErbB3. J Clin Oncol. 2015;33(suppl 3):abstr 384.
– reference: Somasundaram R, Zhang G, Wagner SN, Fukunaga-Kalabis M, Herlyn M. The role of tumor microenvironment in therapy resistance and melanoma progression. Cancer Res. 2015;75 (15 suppl):abstr 420.
– reference: Evdokimova V, Tognon CE, Benatar T, Yang W, Krutikov K, Pollak M, et al. IGFBP7 binds to the IGF-1 receptor and blocks its activation by insulin-like growth factors. Sci Signal. 2012;5(255):ra92. doi:10.1126/scisignal.2003184.
– reference: Schwartz S, Wongvipat J, Trigwell CB, Hancox U, Carver BS, Rodrik-Outmezguine V, et al. Feedback suppression of PI3Kalpha signaling in PTEN-mutated tumors is relieved by selective inhibition of PI3Kbeta. Cancer Cell. 2015;27(1):109–22. doi:10.1016/j.ccell.2014.11.008.
– reference: SellCDumenilGDeveaudCMiuraMCoppolaDDeAngelisTEffect of a null mutation of the insulin-like growth factor I receptor gene on growth and transformation of mouse embryo fibroblastsMol Cell Biol1994146360436121:CAS:528:DyaK2cXktlaiurY%3D10.1128/MCB.14.6.36048196606358728
– reference: Steuerman R, Shevah O, Laron Z. Congenital IGF1 deficiency tends to confer protection against post-natal development of malignancies. Eur J Endocrinol. 2011;164(4):485–9. doi:10.1530/EJE-10-0859.
– reference: Dayyani F, Parikh NU, Varkaris AS, Song JH, Moorthy S, Chatterji T, et al. Combined inhibition of IGF-1R/IR and Src family kinases enhances antitumor effects in prostate cancer by decreasing activated survival pathways. PLoS One. 2012;7(12):e51189. doi:10.1371/journal.pone.0051189.
– reference: Schoffski P, Adkins D, Blay JY, Gil T, Elias AD, Rutkowski P, et al. An open-label, phase 2 study evaluating the efficacy and safety of the anti-IGF-1R antibody cixutumumab in patients with previously treated advanced or metastatic soft-tissue sarcoma or Ewing family of tumours. Eur J Cancer. 2013;49(15):3219–28. doi:10.1016/j.ejca.2013.06.010.
– reference: Beroukhim R, Mermel CH, Porter D, Wei G, Raychaudhuri S, Donovan J, et al. The landscape of somatic copy-number alteration across human cancers. Nature. 2010;463(7283):899–905. doi:10.1038/nature08822.
– reference: BurrowSAndrulisILPollakMBellRSExpression of insulin-like growth factor receptor, IGF-1, and IGF-2 in primary and metastatic osteosarcomaJ Surg Oncol199869121271:CAS:528:DyaK1cXmsF2ltrk%3D10.1002/(SICI)1096-9098(199809)69:1<21::AID-JSO5>3.0.CO;2-M9762887
– reference: Zhang T, Shen H, Dong W, Qu X, Liu Q, Du J. Antitumor effects and molecular mechanisms of figitumumab, a humanized monoclonal antibody to IGF-1 receptor, in esophageal carcinoma. Sci Rep. 2014;4:6855. doi:10.1038/srep06855.
– reference: WernerHRobertsCTJrRauscherFJ3rdLeRoithDRegulation of insulin-like growth factor I receptor gene expression by the Wilms’ tumor suppressor WT1J Mol Neurosci1996721111231:CAS:528:DyaK28Xlt1Wmsbg%3D10.1007/BF027367918873895
– reference: Sharon SM, Pozniak Y, Geiger T, Werner H. TMPRSS2-ERG fusion protein regulates insulin-like growth factor-1 receptor (IGF1R) gene expression in prostate cancer: involvement of transcription factor Sp1. Oncotarget. 2016;7(32):51375–92. doi:10.18632/oncotarget.9837.
– reference: Reidy-Lagunes DL, Vakiani E, Segal MF, Hollywood EM, Tang LH, Solit DB, et al. A phase 2 study of the insulin-like growth factor-1 receptor inhibitor MK-0646 in patients with metastatic, well-differentiated neuroendocrine tumors. Cancer. 2012;118(19):4795–800. doi:10.1002/cncr.27459.
– reference: Malempati S, Weigel B, Ingle AM, Ahern CH, Carroll JM, Roberts CT, et al. Phase I/II trial and pharmacokinetic study of cixutumumab in pediatric patients with refractory solid tumors and Ewing sarcoma: a report from the Children’s Oncology group. J Clin Oncol. 2012;30(3):256–62. doi:10.1200/JCO.2011.37.4355.
– reference: LoRusso PM. Inhibition of the PI3K/AKT/mTOR pathway in solid tumors. J Clin Oncol. 2016;34(31):3803–15. doi:10.1200/JCO.2014.59.0018.
– reference: Lovly CM, McDonald NT, Chen H, Ortiz-Cuaran S, Heukamp LC, Yan Y, et al. Rationale for co-targeting IGF-1R and ALK in ALK fusion-positive lung cancer. Nat Med. 2014;20(9):1027–34. doi:10.1038/nm.3667.
– reference: Friedbichler K, Hofmann MH, Kroez M, Ostermann E, Lamche HR, Koessl C, et al. Pharmacodynamic and antineoplastic activity of BI 836845, a fully human IGF ligand-neutralizing antibody, and mechanistic rationale for combination with rapamycin. Mol Cancer Ther. 2014;13(2):399–409. doi:10.1158/1535-7163.MCT-13-0598.
– reference: Min HY, Yun HJ, Lee JS, Lee HJ, Cho J, Jang HJ, et al. Targeting the insulin-like growth factor receptor and Src signaling network for the treatment of non-small cell lung cancer. Mol Cancer. 2015;14:113. doi:10.1186/s12943-015-0392-3.
– reference: Naing A, Kurzrock R, Burger A, Gupta S, Lei X, Busaidy N, et al. Phase I trial of cixutumumab combined with temsirolimus in patients with advanced cancer. Clin Cancer Res. 2011;17(18):6052–60. doi:10.1158/1078-0432.CCR-10-2979.
– reference: Mulvihill MJ, Cooke A, Rosenfeld-Franklin M, Buck E, Foreman K, Landfair D, et al. Discovery of OSI-906: a selective and orally efficacious dual inhibitor of the IGF-1 receptor and insulin receptor. Future Med Chem. 2009;1(6):1153–71. doi:10.4155/fmc.09.89.
– reference: Ireland L, Santos A, Ahmed MS, Rainer C, Nielsen SR, Quaranta V, et al. Chemoresistance in pancreatic cancer is driven by stroma-derived insulin-like growth factors. Cancer Res. 2016;76(23):6851–6863. doi:10.1158/0008-5472.CAN-16-1201.
– reference: Wagner LM, Fouladi M, Ahmed A, Krailo MD, Weigel B, DuBois SG, et al. Phase II study of cixutumumab in combination with temsirolimus in pediatric patients and young adults with recurrent or refractory sarcoma: a report from the Children’s Oncology group. Pediatr Blood Cancer. 2015;62(3):440–4. doi:10.1002/pbc.25334.
– reference: Lamhamedi-Cherradi SE, Menegaz BA, Ramamoorthy V, Vishwamitra D, Wang Y, Maywald RL et al. IGF-1R and mTOR blockade: Novel resistance mechanisms and synergistic drug combinations for Ewing Sarcoma. J Natl Cancer Inst. 2016;108(12). doi:10.1093/jnci/djw182.
– reference: Heerboth S, Housman G, Leary M, Longacre M, Byler S, Lapinska K, et al. EMT and tumor metastasis. Clin Transl Med. 2015;4:6. doi:10.1186/s40169-015-0048-3.
– reference: Anderson PM, Bielack SS, Gorlick RG, Skubitz K, Daw NC, Herzog CE, et al. A phase II study of clinical activity of SCH 717454 (robatumumab) in patients with relapsed osteosarcoma and Ewing sarcoma. Pediatr Blood Cancer. 2016;63(10):1761–70. doi:10.1002/pbc.26087.
– reference: Cao H, Dong W, Shen H, Xu J, Zhu L, Liu Q, et al. Combinational therapy enhances the effects of Anti-IGF-1R mAb Figitumumab to target small cell lung cancer. PLoS One. 2015;10(8):e0135844. doi:10.1371/journal.pone.0135844.
– reference: Sachdev D, Singh R, Fujita-Yamaguchi Y, Yee D. Down-regulation of insulin receptor by antibodies against the type I insulin-like growth factor receptor: implications for anti-insulin-like growth factor therapy in breast cancer. Cancer Res. 2006;66(4):2391–402. doi:10.1158/0008-5472.CAN-05-3126.
– reference: Zhang H, Pelzer AM, Kiang DT, Yee D. Down-regulation of type I insulin-like growth factor receptor increases sensitivity of breast cancer cells to insulin. Cancer Res. 2007;67(1):391–7. doi:10.1158/0008-5472.CAN-06-1712.
– reference: Weickhardt A, Doebele R, Oton A, Lettieri J, Maxson D, Reynolds M, et al. A phase I/II study of erlotinib in combination with the anti-insulin-like growth factor-1 receptor monoclonal antibody IMC-A12 (cixutumumab) in patients with advanced non-small cell lung cancer. J Thorac Oncol. 2012;7(2):419–26. doi:10.1097/JTO.0b013e31823c5b11.
– reference: Zanella ER, Galimi F, Sassi F, Migliardi G, Cottino F, Leto SM, et al. IGF2 is an actionable target that identifies a distinct subpopulation of colorectal cancer patients with marginal response to anti-EGFR therapies. Sci Transl Med. 2015;7(272):272ra12. doi:10.1126/scitranslmed.3010445.
– reference: Suda K, Mizuuchi H, Sato K, Takemoto T, Iwasaki T, Mitsudomi T. The insulin-like growth factor 1 receptor causes acquired resistance to erlotinib in lung cancer cells with the wild-type epidermal growth factor receptor. Int J Cancer. 2014;135(4):1002–6. doi:10.1002/ijc.28737.
– reference: Buck E, Gokhale PC, Koujak S, Brown E, Eyzaguirre A, Tao N, et al. Compensatory insulin receptor (IR) activation on inhibition of insulin-like growth factor-1 receptor (IGF-1R): rationale for cotargeting IGF-1R and IR in cancer. Mol Cancer Ther. 2010;9(10):2652–64. doi:10.1158/1535-7163.MCT-10-0318.
– reference: TrojanJJohnsonTRRudinSDIlanJTykocinskiMLIlanJTreatment and prevention of rat glioblastoma by immunogenic C6 cells expressing antisense insulin-like growth factor I RNAScience1993259509194971:CAS:528:DyaK3sXptl2itw%3D%3D10.1126/science.84185028418502
– reference: Sanchez-Lopez E, Flashner-Abramson E, Shalapour S, Zhong Z, Taniguchi K, Levitzki A, et al. Targeting colorectal cancer via its microenvironment by inhibiting IGF-1 receptor-insulin receptor substrate and STAT3 signaling. Oncogene. 2016;35(20):2634–44. doi:10.1038/onc.2015.326.
– reference: Baselga J, Morales S, Awada A, Blum J, Tan A, Ewertz M, et al. A phase 2 study of ridaforolimus (RIDA) and dalotuzumab (DALO) in estrogen receptor positive (ER+) breast cancer. Cancer Res. 2013;73(24 suppl)abstr: P2-16-04. doi:10.1158/0008-5472.sabcs13-p2-16-04.
– reference: Bhaskar PT, Hay N. The two TORCs and Akt. Dev Cell. 2007;12(4):487–502. doi: 10.1016/j.devcel.2007.03.020.
– reference: Riedemann J, Macaulay VM. IGF1R signalling and its inhibition. Endocr Relat Cancer. 2006;13(suppl 1):S33–43. doi:10.1677/erc.1.01280.
– reference: Rochester MA, Riedemann J, Hellawell GO, Brewster SF, Macaulay VM. Silencing of the IGF1R gene enhances sensitivity to DNA-damaging agents in both PTEN wild-type and mutant human prostate cancer. Cancer Gene Ther. 2005;12(1):90–100. doi:10.1038/sj.cgt.7700775.
– ident: 514_CR181
  doi: 10.1038/nature08768
– ident: 514_CR2
  doi: 10.1016/j.gendis.2014.10.004
– ident: 514_CR129
  doi: 10.1158/1535-7163.MCT-12-0618
– ident: 514_CR29
  doi: 10.3389/fendo.2014.00010
– ident: 514_CR98
  doi: 10.1093/annonc/mdq349
– volume: 32
  start-page: abstr 2617
  issue: 5 suppl
  year: 2014
  ident: 514_CR78
  publication-title: J Clin Oncol
  doi: 10.1200/jco.2014.32.15_suppl.2617
– volume: 69
  start-page: 21
  issue: 1
  year: 1998
  ident: 514_CR19
  publication-title: J Surg Oncol
  doi: 10.1002/(SICI)1096-9098(199809)69:1<21::AID-JSO5>3.0.CO;2-M
– ident: 514_CR104
  doi: 10.1038/nm.3667
– ident: 514_CR86
  doi: 10.1634/theoncologist.2016-0220
– ident: 514_CR215
  doi: 10.15252/emmm.201303376
– ident: 514_CR122
  doi: 10.1158/1078-0432.CCR-12-1840
– ident: 514_CR12
  doi: 10.1007/s11523-012-0248-3
– ident: 514_CR85
  doi: 10.1002/cncr.28728
– ident: 514_CR128
  doi: 10.1038/onc.2016.248
– ident: 514_CR218
  doi: 10.1111/cei.12374
– ident: 514_CR174
  doi: 10.1016/j.ccell.2014.11.008
– ident: 514_CR80
  doi: 10.1002/jcp.24217
– ident: 514_CR126
  doi: 10.1158/1535-7163.MCT-13-0442-T
– ident: 514_CR156
  doi: 10.1158/1078-0432.CCR-14-0940
– ident: 514_CR205
  doi: 10.1056/NEJMoa1501824
– ident: 514_CR183
  doi: 10.1038/onc.2015.488
– volume: 92
  start-page: 12146
  issue: 26
  year: 1995
  ident: 514_CR37
  publication-title: Proc Natl Acad Sci U S A
  doi: 10.1073/pnas.92.26.12146
– ident: 514_CR166
  doi: 10.1126/science.aad3018
– ident: 514_CR167
  doi: 10.1038/bjc.2015.242
– ident: 514_CR198
  doi: 10.1172/JCI41824
– ident: 514_CR54
  doi: 10.1038/srep06855
– ident: 514_CR72
  doi: 10.1016/j.beem.2008.08.004
– ident: 514_CR102
  doi: 10.1186/1471-2407-13-41
– ident: 514_CR56
  doi: 10.1158/1535-7163.MCT-05-0048
– ident: 514_CR193
  doi: 10.1530/ERC-15-0002
– volume: 7
  start-page: 331
  issue: 3
  year: 1993
  ident: 514_CR36
  publication-title: Genes Dev
  doi: 10.1101/gad.7.3.331
– ident: 514_CR192
  doi: 10.1002/pbc.25334
– ident: 514_CR105
  doi: 10.1158/1078-0432.CCR-15-1677
– ident: 514_CR33
  doi: 10.1016/j.radonc.2012.03.009
– ident: 514_CR68
  doi: 10.1158/0008-5472.CAN-05-3126
– volume: 56
  start-page: 1761
  issue: 8
  year: 1996
  ident: 514_CR20
  publication-title: Cancer Res
– ident: 514_CR3
  doi: 10.1038/nrc3215
– ident: 514_CR81
  doi: 10.1200/JCO.2011.37.4355
– ident: 514_CR143
  doi: 10.1002/stem.1328
– ident: 514_CR160
  doi: 10.1158/0008-5472.CAN-13-2923
– ident: 514_CR58
  doi: 10.1002/cncr.27459
– ident: 514_CR27
  doi: 10.1053/j.gastro.2016.09.001
– ident: 514_CR48
  doi: 10.1007/s00018-013-1514-y
– ident: 514_CR118
  doi: 10.1200/JCO.2011.37.2359
– ident: 514_CR189
  doi: 10.1016/j.cllc.2016.07.007
– ident: 514_CR53
  doi: 10.1158/1535-7163.MCT-08-1171
– ident: 514_CR169
  doi: 10.1093/jnci/djv258
– volume: 259
  start-page: 94
  issue: 5091
  year: 1993
  ident: 514_CR213
  publication-title: Science
  doi: 10.1126/science.8418502
– ident: 514_CR5
  doi: 10.1158/1078-0432.CCR-07-4879
– volume: 28
  start-page: abstr 3104
  issue: suppl 15
  year: 2010
  ident: 514_CR94
  publication-title: J Clin Oncol
  doi: 10.1200/jco.2010.28.15_suppl.3104
– ident: 514_CR46
  doi: 10.1126/scisignal.2000628
– ident: 514_CR210
  doi: 10.1158/2159-8290.CD-14-0477
– ident: 514_CR132
  doi: 10.1038/sj.cgt.7700775
– ident: 514_CR141
  doi: 10.18632/oncotarget.5631
– ident: 514_CR130
  doi: 10.1016/j.ejca.2012.05.009
– ident: 514_CR92
  doi: 10.1158/1078-0432.CCR-15-0588
– ident: 514_CR168
  doi: 10.1200/JCO.2013.54.4932
– ident: 514_CR24
  doi: 10.1016/j.ccell.2014.11.013
– ident: 514_CR60
  doi: 10.1158/1535-7163.MCT-09-0499
– ident: 514_CR123
  doi: 10.1093/annonc/mdv027
– ident: 514_CR219
  doi: 10.1016/j.yexcr.2015.05.015
– ident: 514_CR41
  doi: 10.1016/j.devcel.2007.03.020
– ident: 514_CR146
  doi: 10.3390/vaccines3030519
– ident: 514_CR114
  doi: 10.1038/nature08822
– volume: 62
  start-page: 200
  issue: 1
  year: 2002
  ident: 514_CR145
  publication-title: Cancer Res
– ident: 514_CR127
  doi: 10.1158/1535-7163.MCT-09-0381
– ident: 514_CR178
  doi: 10.1158/1078-0432.CCR-11-2381
– ident: 514_CR187
  doi: 10.1158/1078-0432.CCR-10-2621
– ident: 514_CR9
  doi: 10.1038/onc.2012.538
– ident: 514_CR51
  doi: 10.3389/fphar.2013.00030
– ident: 514_CR175
  doi: 10.1186/s12885-016-2847-3
– ident: 514_CR222
– ident: 514_CR59
  doi: 10.1016/j.jhep.2013.09.008
– ident: 514_CR45
  doi: 10.1210/en.2012-2165
– ident: 514_CR148
  doi: 10.1371/journal.pone.0051189
– ident: 514_CR119
  doi: 10.1007/s10637-011-9715-4
– ident: 514_CR170
  doi: 10.1200/jco.2016.34.4_suppl.tps481
– ident: 514_CR101
  doi: 10.3892/ijo.2016.3401
– ident: 514_CR155
  doi: 10.1200/jco.2005.23.16_suppl.3112
– ident: 514_CR153
  doi: 10.1158/2159-8290.CD-12-0446
– ident: 514_CR52
  doi: 10.1155/2012/804801
– ident: 514_CR162
  doi: 10.1186/s12885-015-1803-y
– ident: 514_CR163
  doi: 10.1038/srep31072
– ident: 514_CR106
  doi: 10.1002/ijc.28737
– ident: 514_CR75
  doi: 10.1158/1078-0432.CCR-14-0114
– ident: 514_CR124
  doi: 10.1158/1538-7445.am2015-ct237
– ident: 514_CR157
  doi: 10.1158/0008-5472.CAN-14-3358
– ident: 514_CR25
  doi: 10.1158/1535-7163.MCT-10-0318
– ident: 514_CR199
  doi: 10.18632/oncotarget.9837
– ident: 514_CR62
  doi: 10.1111/cas.12906
– ident: 514_CR116
  doi: 10.1200/JCO.2010.33.0670
– ident: 514_CR31
  doi: 10.1038/onc.2013.460
– ident: 514_CR67
  doi: 10.1016/j.ejca.2007.03.009
– ident: 514_CR203
  doi: 10.1093/annonc/mdv222
– volume: 32
  start-page: 3029
  issue: 8
  year: 2012
  ident: 514_CR142
  publication-title: Anticancer Res
– volume: 31
  start-page: abstr 5515
  issue: suppl
  year: 2013
  ident: 514_CR93
  publication-title: J Clin Oncol
  doi: 10.1200/jco.2013.31.15_suppl.5515
– ident: 514_CR71
  doi: 10.1158/1078-0432.CCR-10-3336
– ident: 514_CR176
  doi: 10.1093/jnci/djw182
– volume: 29
  start-page: abstr 7584
  issue: suppl
  year: 2011
  ident: 514_CR125
  publication-title: J Clin Oncol
  doi: 10.1200/jco.2011.29.15_suppl.7584
– ident: 514_CR185
  doi: 10.1200/jco.2010.28.15_suppl.3026
– ident: 514_CR65
  doi: 10.1158/0008-5472.CAN-10-2274
– ident: 514_CR1
  doi: 10.1155/2015/538019
– ident: 514_CR107
  doi: 10.1126/scitranslmed.3010445
– ident: 514_CR15
  doi: 10.1002/gcc.10157
– ident: 514_CR96
  doi: 10.1158/1078-0432.CCR-14-0265
– ident: 514_CR120
  doi: 10.1097/JTO.0b013e31823c5b11
– ident: 514_CR201
  doi: 10.1200/JCO.2016.34.15_suppl.530
– ident: 514_CR138
  doi: 10.1158/1535-7163.MCT-12-0447
– ident: 514_CR43
  doi: 10.1158/0008-5472.CAN-10-0052
– ident: 514_CR139
  doi: 10.1158/0008-5472.CAN-16-1201
– volume: 30
  start-page: abstr 4054
  issue: suppl
  year: 2012
  ident: 514_CR121
  publication-title: J Clin Oncol
– ident: 514_CR40
  doi: 10.1038/35060032
– ident: 514_CR73
  doi: 10.1007/s10911-008-9104-6
– ident: 514_CR10
  doi: 10.4081/oncol.2013.e3
– ident: 514_CR133
  doi: 10.1158/0008-5472.sabcs-09-402
– ident: 514_CR44
  doi: 10.1016/j.bbrc.2010.12.038
– ident: 514_CR112
  doi: 10.18632/oncotarget.9100
– ident: 514_CR110
  doi: 10.1126/science.1235122
– ident: 514_CR217
  doi: 10.1189/jlb.0404248
– ident: 514_CR152
  doi: 10.1158/1078-0432.CCR-13-0145
– ident: 514_CR195
  doi: 10.1210/jc.2012-3856
– ident: 514_CR11
  doi: 10.1158/1535-7163.MCT-06-0080
– ident: 514_CR191
  doi: 10.1007/s10637-014-0177-3
– ident: 514_CR39
  doi: 10.1038/nm759
– ident: 514_CR23
  doi: 10.1530/ERC-13-0231
– ident: 514_CR30
  doi: 10.1186/s40169-015-0048-3
– ident: 514_CR214
  doi: 10.2337/db11-1776
– volume: 14
  start-page: 3604
  issue: 6
  year: 1994
  ident: 514_CR13
  publication-title: Mol Cell Biol
  doi: 10.1128/MCB.14.6.3604
– volume: 5
  start-page: 2503
  issue: 10
  year: 1986
  ident: 514_CR6
  publication-title: EMBO J
  doi: 10.1002/j.1460-2075.1986.tb04528.x
– ident: 514_CR182
  doi: 10.3389/fendo.2012.00021
– ident: 514_CR208
  doi: 10.1056/NEJMc1509660
– ident: 514_CR18
  doi: 10.1530/EJE-10-0859
– ident: 514_CR173
– ident: 514_CR196
  doi: 10.1158/0008-5472.CAN-04-1837
– ident: 514_CR84
  doi: 10.1200/JCO.2009.23.6745
– ident: 514_CR204
  doi: 10.1056/NEJMoa1507643
– ident: 514_CR42
  doi: 10.1038/sj.onc.1210715
– ident: 514_CR57
  doi: 10.1158/1535-7163.MCT-13-0255
– volume: 54
  start-page: 2218
  issue: 8
  year: 1994
  ident: 514_CR212
  publication-title: Cancer Res
– ident: 514_CR180
  doi: 10.1038/364308a0
– ident: 514_CR206
  doi: 10.1016/S0140-6736(15)01281-7
– ident: 514_CR186
  doi: 10.1158/1078-0432.CCR-10-2979
– ident: 514_CR172
  doi: 10.18632/oncotarget.8484
– ident: 514_CR202
  doi: 10.1200/JCO.2013.54.8404
– ident: 514_CR137
  doi: 10.1158/0008-5472.CAN-12-2066
– ident: 514_CR91
  doi: 10.1007/s00280-009-1083-9
– ident: 514_CR216
  doi: 10.1242/dmm.015362
– ident: 514_CR8
  doi: 10.1038/nrc3720
– ident: 514_CR136
  doi: 10.1172/JCI34588
– ident: 514_CR76
  doi: 10.1007/s10637-014-0170-x
– ident: 514_CR207
  doi: 10.1056/NEJMoa1003466
– ident: 514_CR220
  doi: 10.1016/j.jhep.2014.11.011
– ident: 514_CR177
  doi: 10.1200/JCO.2014.59.0018
– ident: 514_CR74
  doi: 10.1158/1535-7163.MCT-14-0144
– ident: 514_CR22
  doi: 10.1371/journal.pone.0135844
– ident: 514_CR115
  doi: 10.1200/JCO.2009.24.6611
– ident: 514_CR221
  doi: 10.1158/1538-7445.AM2015-420
– ident: 514_CR103
  doi: 10.1002/mc.22342
– volume: 20
  start-page: 2912
  issue: 17
  year: 2014
  ident: 514_CR49
  publication-title: Curr Pharm Des
  doi: 10.2174/13816128113199990596
– ident: 514_CR95
  doi: 10.1158/1078-0432.CCR-07-1118
– volume: 5
  start-page: 231
  issue: 3
  year: 2004
  ident: 514_CR64
  publication-title: Cancer Cell
  doi: 10.1016/S1535-6108(04)00051-0
– ident: 514_CR32
  doi: 10.1158/1535-7163.MCT-12-1067
– ident: 514_CR134
  doi: 10.1158/1078-0432.CCR-07-0648
– ident: 514_CR21
  doi: 10.1016/j.ctrv.2014.07.004
– ident: 514_CR70
– ident: 514_CR190
  doi: 10.1158/1078-0432.CCR-13-2752
– ident: 514_CR14
  doi: 10.1677/erc.1.01280
– ident: 514_CR144
  doi: 10.1080/15384101.2016.1160982
– ident: 514_CR188
  doi: 10.1158/1078-0432.CCR-15-2218
– ident: 514_CR194
  doi: 10.1158/0008-5472.sabcs13-p2-16-04
– ident: 514_CR69
  doi: 10.4161/onci.20925
– ident: 514_CR50
  doi: 10.1038/nature11249
– ident: 514_CR111
  doi: 10.1002/ijc.24623
– ident: 514_CR154
  doi: 10.1186/1471-2407-13-170
– ident: 514_CR66
  doi: 10.1158/1535-7163.MCT-13-0598
– ident: 514_CR100
  doi: 10.1186/1476-4598-13-71
– ident: 514_CR63
  doi: 10.18632/oncotarget.8013
– ident: 514_CR158
  doi: 10.1038/onc.2015.229
– ident: 514_CR147
  doi: 10.1158/1535-7163.MCT-11-0205
– ident: 514_CR117
  doi: 10.1200/JCO.2010.34.0000
– ident: 514_CR97
  doi: 10.1002/pbc.26087
– ident: 514_CR209
  doi: 10.1016/S1470-2045(15)00083-2
– ident: 514_CR82
  doi: 10.1016/j.ejca.2013.06.010
– ident: 514_CR61
  doi: 10.4155/fmc.09.89
– ident: 514_CR135
  doi: 10.2174/1574362409666140206221931
– ident: 514_CR55
  doi: 10.1158/1078-0432.CCR-09-3220
– ident: 514_CR109
  doi: 10.1158/0008-5472.CAN-14-0970
– ident: 514_CR89
  doi: 10.1200/jco.2015.33.3_suppl.384
– ident: 514_CR161
  doi: 10.1126/scisignal.2004014
– ident: 514_CR7
  doi: 10.1021/jm9002395
– ident: 514_CR159
  doi: 10.1038/onc.2015.326
– ident: 514_CR179
  doi: 10.1038/370527a0
– ident: 514_CR171
  doi: 10.1158/1535-7163.MCT-16-0313
– ident: 514_CR34
  doi: 10.3389/fendo.2015.00077
– ident: 514_CR47
  doi: 10.3390/cancers2020233
– ident: 514_CR99
  doi: 10.1016/j.ccr.2010.10.031
– ident: 514_CR140
  doi: 10.1158/1078-0432.CCR-08-1401
– ident: 514_CR17
  doi: 10.1126/scitranslmed.3001845
– ident: 514_CR108
  doi: 10.3389/fendo.2015.00092
– ident: 514_CR151
  doi: 10.1172/JCI57909
– ident: 514_CR4
  doi: 10.1126/scisignal.2003184
– ident: 514_CR88
  doi: 10.1200/jco.2013.31.15_suppl.6030
– ident: 514_CR77
  doi: 10.1200/jco.2014.32.15_suppl.2622
– ident: 514_CR131
  doi: 10.1002/jcb.24080
– ident: 514_CR197
  doi: 10.1016/S1470-2045(13)70026-3
– ident: 514_CR26
  doi: 10.1158/0008-5472.CAN-06-1712
– ident: 514_CR87
  doi: 10.1093/annonc/mdr574
– ident: 514_CR200
  doi: 10.1016/S1470-2045(13)70019-6
– volume: 65
  start-page: 1053
  issue: 6
  year: 1991
  ident: 514_CR35
  publication-title: Cell
  doi: 10.1016/0092-8674(91)90557-F
– ident: 514_CR164
  doi: 10.18632/oncotarget.10862
– ident: 514_CR28
  doi: 10.1016/j.cell.2011.02.013
– volume: 27
  start-page: abstr 2790
  issue: suppl
  year: 2016
  ident: 514_CR79
  publication-title: Ann Oncol
– ident: 514_CR90
  doi: 10.1007/s00280-014-2391-2
– ident: 514_CR113
  doi: 10.1158/1078-0432.CCR-09-2719
– ident: 514_CR38
  doi: 10.1038/378785a0
– volume: 7
  start-page: 111
  issue: 2
  year: 1996
  ident: 514_CR16
  publication-title: J Mol Neurosci
  doi: 10.1007/BF02736791
– ident: 514_CR150
  doi: 10.1016/j.neo.2015.03.001
– ident: 514_CR83
  doi: 10.1016/S1470-2045(09)70354-7
– ident: 514_CR165
  doi: 10.18632/oncotarget.3425
– ident: 514_CR184
  doi: 10.1038/bjc.2014.497
– ident: 514_CR211
  doi: 10.1200/jco.2001.19.8.2189
– ident: 514_CR149
  doi: 10.1186/s12943-015-0392-3
SSID ssj0047250
Score 2.4907935
SecondaryResourceType review_article
Snippet Despite a strong preclinical rationale for targeting the insulin-like growth factor (IGF) axis in cancer, clinical studies of IGF-1 receptor (IGF-1R)-targeted...
SourceID pubmedcentral
proquest
pubmed
crossref
springer
SourceType Open Access Repository
Aggregation Database
Index Database
Enrichment Source
Publisher
StartPage 571
SubjectTerms Antineoplastic Agents - pharmacology
Biomedicine
Cancer
Drug Resistance, Neoplasm - physiology
Humans
Insulin
Insulin-like growth factors
Ligands
Medicine
Medicine & Public Health
Metabolism
Neoplasms - drug therapy
Oncology
Receptor, IGF Type 1 - antagonists & inhibitors
Review
Review Article
Targeted cancer therapy
Treatment resistance
SummonAdditionalLinks – databaseName: SpringerLINK Contemporary 1997-Present
  dbid: RSV
  link: http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1Jb9UwEB5BQYhLWQsPChokDiyylM0bt6oipRKUqhTUW-Tn2GpElVe9pcCZP87YSV55FJDgGGWcxZ7ls2b8DcBTq40ks7HMFbxgBSFYpnJrWeosLXgtEi-6ZhNyb08dHen9_hz3bKh2H1KS0VOfH3ajUBNqfyQLnN2MX4YrFO1UsMaDD58G91vIjHenIKVghO3FkMr83SNWg9EFhHmxUPKXbGkMQuWN__r8m7DeY07c6pTkFlxy7W249q7Pqt-B77tdQTp723x2uEMb8_kxlrERDz7b3Smf4z7hxC_mGx7GunF6LTYtbgeFmb7Cg8mJw4lHgpJI0rj1tZmhaWt8fxrA_aKNpK1I6BjLyGCC5IRoQx51AvtCxrvwsXx9uP2G9c0ZmOW5mDOvcs81zbXIA-vcWI2lSb2Uee2ddDwzSts6L3wqx4nw0nDpM2dDxNRpXRRFvgFr7aR19wGF417pWhmZmJCmNWGPldKFd2NyMXYEybBKle2Zy0MDjZPqnHM5TG5Fk1uFya34CF4sh5x2tB1_E94clr7qLXhWpZoUV0tyUCN4srxNthcSKqZ1k0WQyWMTL04y9zpNWb4tU4rQaaJHIFd0aCkQeL1X77TNceT3DpBWCBr5ctCknz7rTz_x4J-kH8L1LKhirErchLX5dOEewVV7Nm9m08fRoH4Azm0ZSw
  priority: 102
  providerName: Springer Nature
Title Insulin-Like Growth Factor (IGF) Pathway Targeting in Cancer: Role of the IGF Axis and Opportunities for Future Combination Studies
URI https://link.springer.com/article/10.1007/s11523-017-0514-5
https://www.ncbi.nlm.nih.gov/pubmed/28815409
https://www.proquest.com/docview/1941897196
https://www.proquest.com/docview/1930486056
https://pubmed.ncbi.nlm.nih.gov/PMC5610669
Volume 12
WOSCitedRecordID wos000411741500002&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D
hasFullText 1
inHoldings 1
isFullTextHit
isPrint
journalDatabaseRights – providerCode: PRVPQU
  databaseName: Consumer Health Database
  customDbUrl:
  eissn: 1776-260X
  dateEnd: 20171231
  omitProxy: false
  ssIdentifier: ssj0047250
  issn: 1776-2596
  databaseCode: M0R
  dateStart: 20060101
  isFulltext: true
  titleUrlDefault: https://search.proquest.com/familyhealth
  providerName: ProQuest
– providerCode: PRVPQU
  databaseName: Nursing & Allied Health Database
  customDbUrl:
  eissn: 1776-260X
  dateEnd: 20171231
  omitProxy: false
  ssIdentifier: ssj0047250
  issn: 1776-2596
  databaseCode: 7RV
  dateStart: 20060101
  isFulltext: true
  titleUrlDefault: https://search.proquest.com/nahs
  providerName: ProQuest
– providerCode: PRVPQU
  databaseName: ProQuest Central
  customDbUrl:
  eissn: 1776-260X
  dateEnd: 20171231
  omitProxy: false
  ssIdentifier: ssj0047250
  issn: 1776-2596
  databaseCode: BENPR
  dateStart: 20060101
  isFulltext: true
  titleUrlDefault: https://www.proquest.com/central
  providerName: ProQuest
– providerCode: PRVPQU
  databaseName: ProQuest Health & Medical Collection
  customDbUrl:
  eissn: 1776-260X
  dateEnd: 20171231
  omitProxy: false
  ssIdentifier: ssj0047250
  issn: 1776-2596
  databaseCode: 7X7
  dateStart: 20060101
  isFulltext: true
  titleUrlDefault: https://search.proquest.com/healthcomplete
  providerName: ProQuest
– providerCode: PRVAVX
  databaseName: SpringerLINK Contemporary 1997-Present
  customDbUrl:
  eissn: 1776-260X
  dateEnd: 99991231
  omitProxy: false
  ssIdentifier: ssj0047250
  issn: 1776-2596
  databaseCode: RSV
  dateStart: 20060101
  isFulltext: true
  titleUrlDefault: https://link.springer.com/search?facet-content-type=%22Journal%22
  providerName: Springer Nature
link http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwpV1Lb9QwELboFiEuvKELpTISBx6yyMuxwwWVqimV6LJaSrW3yOvYatQqWfbB48wfZ8ZxtiwVvXCxFGWixJmHP2cm3xDyXGdKgNtoZhKesAQQLJOx1iw0GhRepoFN22YTYjCQ43E29B_c5r6ssouJLlCXjcZv5G9gsx3KTIDBvJt-Zdg1CrOrvoXGBtlEprKkRzbf7w-Goy4WJyLi7S-RImUA9NMur-l-noOlC2uJBEMOcMbXV6ZLcPNy1eRfqVO3IuW3_3cud8gtj0Xpbms8d8k1U98jN458tv0--XXYFqqzj9WZoQewYV-c0tw16KEvDg_yl3QI-PG7-kmPXT05PCWtarqHhjR7S0fNuaGNpQAxKUjT3R_VnKq6pJ-mCPqXtSNzpYCaae6YTSgEJ9ioO1uhvsDxAfmS7x_vfWC-aQPTPE4XzMrY8gxeexojG91EToQKrRBxaY0wPFIy02Wc2FBMgtQKxYWNjMaVNAvLJEnih6RXN7XZIjQ13MqslEoECtO3CvdeIRxYM4HQo_sk6BRWaM9ojo01zosLLmbUcQE6LlDHBe-TV6tLpi2dx1XC2536Cu_Z8-JCd33ybHUafBITLao2zRJlYtfci4PMo9ZoVneLpATUGmR9ItbMaSWAfN_rZ-rq1PF-I9RNU7jydWd4fzzWvybx-OpJPCE3I3QBV564TXqL2dI8Jdf1t0U1n-2QDTE6wXEs3Ch3vIPB0VGA4-jzyW8K0ipP
linkProvider ProQuest
linkToHtml http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMw1V1Lb9QwELZKQcCF92OhwCCBREEWedtBQqgqbLvqdqmqBfUWEsdWI6pk2QdLz_wffiMzTrJlqeitB45RJi_nm88znvEMY89UnApUG8V1EAY8QAuWS18p7mqFPzyPHBPVzSbEYCAPDuK9Ffar3QtDaZUtJ1qizitFa-Sv0dl2ZSwQMO9G3zh1jaLoattCo4bFjj6eo8s2edt7j__3ued1Pww3t3nTVYCr0I-m3EjfhDHO_JFP5dIymYnUNUL4udFCh14qY5X7gXFF5kRGpKEwnlZE9bGbB0Hg430vsIvI4y6lkIn9zy3zB8IL6w2YIuLoVkRtFNVu1cOJkjKXBKeK4zxcngdPGbenczT_CtTa-a97_X8buRvsWmNpw0atGjfZii5vscu7TS7BbfazV6fh837xVcPWuJpPD6Fr2w_Bi95Wdx320Dqep8cwtNnyOCpQlLBJajJ-A_vVkYbKABrQgNKw8aOYQFrm8HFELs2stKVqAX0C6Nq6LYDUmxX14is06Zt32KdzGYK7bLWsSn2fQaRDI-NcpsJJKTidkmfp4oHRGRKr6jCnBUiimnrt1DbkKDmpNE2YShBTCWEqCTvs5eKSUV2s5CzhtRYuScNbk-QEKx32dHEaGYfCSGmpqxnJ-LZ1WYgy92qQLp7mSYk2uRN3mFiC70KAqpkvnymLQ1vVnAz5KMIrX7VA_-O1_vURD87-iCfsyvZwt5_0e4Odh-yqR-pnEzHX2Op0PNOP2CX1fVpMxo-tIgP7ct74_w0Gan85
linkToPdf http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMw1V1Zb9QwELZKQRUv3MdCgUECiUNWc9oJEkJVS8qqZVlVRepbSBxbjaiSZQ-WPvOv-HXMOMmWpaJvfeAxyuRyvhnPeD7PMPZMxZlEtVFcB2HAA_RgeeQrxV2t8IcXwjGiaTYhB4Po8DAerrBf3V4YolV2NtEa6qJWtEa-gcG2G8USAbNhWlrEcDt5N_rGqYMUZVq7dhoNRHb1yRzDt8nb_jb-6-eel7w_2PrA2w4DXIW-mHIT-SaM0QsQPpVOy6NcZq6R0i-Mljr0sihWhR8YV-aOMDILpfG0IrMfu0UQBD7e9xK7LCk5SLRBZ7-bBQLphc1mTCk4hhiiy6jabXs4aRKLSXKqPs7D5TnxjKN7lq_5V9LWzoXJ9f95FG-wa60HDpuNytxkK7q6xdY-thyD2-xnv6Hn873yq4adcT2fHkFi2xLBi_5O8hKG6DXPsxM4sCx6HCEoK9gi9Rm_gf36WENtAB1rQGnY_FFOIKsK-DSiUGdW2RK2gLECJLaeC6BJzstmURZaWucd9vlChuAuW63qSt9nIHRooriIMulklLTOKOJ08cDoHA2u6jGnA0uq2jru1E7kOD2tQE34ShFfKeErDXvs1eKSUVPE5Dzh9Q46aWvPJukpbnrs6eI0WiJKL2WVrmck49uWZiHK3GsAu3iaF0Xoqztxj8klKC8EqMr58pmqPLLVzsnBFwKvfN2B_o_X-tdHPDj_I56wNYR9utcf7D5kVz3SRMvPXGer0_FMP2JX1PdpORk_tjoN7MtFw_83xuKH1g
openUrl ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Insulin-Like+Growth+Factor+%28IGF%29+Pathway+Targeting+in+Cancer%3A+Role+of+the+IGF+Axis+and+Opportunities+for+Future+Combination+Studies&rft.jtitle=Targeted+oncology&rft.au=Simpson%2C+Aaron&rft.au=Petnga%2C+Wilfride&rft.au=Macaulay%2C+Valentine+M&rft.au=Weyer-Czernilofsky%2C+Ulrike&rft.date=2017-10-01&rft.eissn=1776-260X&rft.volume=12&rft.issue=5&rft.spage=571&rft_id=info:doi/10.1007%2Fs11523-017-0514-5&rft_id=info%3Apmid%2F28815409&rft.externalDocID=28815409
thumbnail_l http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1776-2596&client=summon
thumbnail_m http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1776-2596&client=summon
thumbnail_s http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1776-2596&client=summon