BRAF Mutants Evade ERK-Dependent Feedback by Different Mechanisms that Determine Their Sensitivity to Pharmacologic Inhibition

ERK signaling requires RAS-induced RAF dimerization and is limited by feedback. Activated BRAF mutants evade feedback inhibition of RAS by either of two mechanisms. BRAF V600 mutants are activated monomers when RAS activity is low; all other activating BRAF mutants function as constitutive RAS-indep...

Celý popis

Uložené v:

Podrobná bibliografia
Vydané v:	Cancer cell Ročník 28; číslo 3; s. 370
Hlavní autori:	Yao, Zhan, Torres, Neilawattie M, Tao, Anthony, Gao, Yijun, Luo, Lusong, Li, Qi, de Stanchina, Elisa, Abdel-Wahab, Omar, Solit, David B, Poulikakos, Poulikos I, Rosen, Neal
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	United States 14.09.2015
Predmet:	Cell Line, Tumor Dimerization Drug Resistance, Neoplasm - drug effects Drug Resistance, Neoplasm - genetics Humans MAP Kinase Signaling System - drug effects MAP Kinase Signaling System - genetics Mutation - genetics Protein Kinase Inhibitors - pharmacology Proto-Oncogene Proteins B-raf - antagonists & inhibitors Proto-Oncogene Proteins B-raf - genetics ras Proteins - genetics
ISSN:	1878-3686, 1878-3686
On-line prístup:	Zistit podrobnosti o prístupe
Tagy:	Pridať tag Žiadne tagy, Buďte prvý, kto otaguje tento záznam!

Abstract	ERK signaling requires RAS-induced RAF dimerization and is limited by feedback. Activated BRAF mutants evade feedback inhibition of RAS by either of two mechanisms. BRAF V600 mutants are activated monomers when RAS activity is low; all other activating BRAF mutants function as constitutive RAS-independent dimers. RAF inhibitors effectively inhibit mutant monomers, but not dimers; their binding to one site in the dimer significantly reduces their affinity for the second. Tumors with non-V600E BRAF mutants are insensitive to these drugs, and increased expression of BRAF V600E dimers causes acquired resistance. A compound that equally inhibits both sites of mutant RAF dimers inhibits tumors driven by either class of mutants or those BRAF V600E tumors with dimer-dependent acquired resistance to monomer-specific inhibitors.
AbstractList	ERK signaling requires RAS-induced RAF dimerization and is limited by feedback. Activated BRAF mutants evade feedback inhibition of RAS by either of two mechanisms. BRAF V600 mutants are activated monomers when RAS activity is low; all other activating BRAF mutants function as constitutive RAS-independent dimers. RAF inhibitors effectively inhibit mutant monomers, but not dimers; their binding to one site in the dimer significantly reduces their affinity for the second. Tumors with non-V600E BRAF mutants are insensitive to these drugs, and increased expression of BRAF V600E dimers causes acquired resistance. A compound that equally inhibits both sites of mutant RAF dimers inhibits tumors driven by either class of mutants or those BRAF V600E tumors with dimer-dependent acquired resistance to monomer-specific inhibitors.ERK signaling requires RAS-induced RAF dimerization and is limited by feedback. Activated BRAF mutants evade feedback inhibition of RAS by either of two mechanisms. BRAF V600 mutants are activated monomers when RAS activity is low; all other activating BRAF mutants function as constitutive RAS-independent dimers. RAF inhibitors effectively inhibit mutant monomers, but not dimers; their binding to one site in the dimer significantly reduces their affinity for the second. Tumors with non-V600E BRAF mutants are insensitive to these drugs, and increased expression of BRAF V600E dimers causes acquired resistance. A compound that equally inhibits both sites of mutant RAF dimers inhibits tumors driven by either class of mutants or those BRAF V600E tumors with dimer-dependent acquired resistance to monomer-specific inhibitors. ERK signaling requires RAS-induced RAF dimerization and is limited by feedback. Activated BRAF mutants evade feedback inhibition of RAS by either of two mechanisms. BRAF V600 mutants are activated monomers when RAS activity is low; all other activating BRAF mutants function as constitutive RAS-independent dimers. RAF inhibitors effectively inhibit mutant monomers, but not dimers; their binding to one site in the dimer significantly reduces their affinity for the second. Tumors with non-V600E BRAF mutants are insensitive to these drugs, and increased expression of BRAF V600E dimers causes acquired resistance. A compound that equally inhibits both sites of mutant RAF dimers inhibits tumors driven by either class of mutants or those BRAF V600E tumors with dimer-dependent acquired resistance to monomer-specific inhibitors.
Author	Solit, David B Tao, Anthony Yao, Zhan de Stanchina, Elisa Abdel-Wahab, Omar Li, Qi Poulikakos, Poulikos I Torres, Neilawattie M Gao, Yijun Luo, Lusong Rosen, Neal
Author_xml	– sequence: 1 givenname: Zhan surname: Yao fullname: Yao, Zhan organization: Program in Molecular Pharmacology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA – sequence: 2 givenname: Neilawattie M surname: Torres fullname: Torres, Neilawattie M organization: Program in Molecular Pharmacology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA – sequence: 3 givenname: Anthony surname: Tao fullname: Tao, Anthony organization: College of Arts and Sciences, New York University, New York, NY 10003, USA – sequence: 4 givenname: Yijun surname: Gao fullname: Gao, Yijun organization: Program in Molecular Pharmacology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA – sequence: 5 givenname: Lusong surname: Luo fullname: Luo, Lusong organization: BeiGene (Beijing) Co., Ltd., No. 30 Science Park Road, Zhong-Guan-Cun Life Science Park, Changping District, Beijing 102206, China – sequence: 6 givenname: Qi surname: Li fullname: Li, Qi organization: Program in Molecular Pharmacology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA – sequence: 7 givenname: Elisa surname: de Stanchina fullname: de Stanchina, Elisa organization: Program in Molecular Pharmacology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA – sequence: 8 givenname: Omar surname: Abdel-Wahab fullname: Abdel-Wahab, Omar organization: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA – sequence: 9 givenname: David B surname: Solit fullname: Solit, David B organization: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA – sequence: 10 givenname: Poulikos I surname: Poulikakos fullname: Poulikakos, Poulikos I organization: Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA – sequence: 11 givenname: Neal surname: Rosen fullname: Rosen, Neal email: rosenn@mskcc.org organization: Program in Molecular Pharmacology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Center for Mechanism Based Therapeutics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Electronic address: rosenn@mskcc.org
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/26343582$$D View this record in MEDLINE/PubMed
BookMark	eNpNkEtPwzAQhC1URB_wC5CQj1wS_Ggc91j6gIpWoFLOlWNviEvjlNit1Au_nVSAxFx2NPtppZ0uarnKAULXlMSUUHG3ibWG7TZmhCYxkTEh9Ax1qExlxIUUrX--jbrebxpA0HRwgdpM8D5PJOugr_vlcIoX-6Bc8HhyUAbwZPkUjWEHzoALeApgMqU_cHbEY5vnUJ_SBehCOetLj0OhAh5DgLq0DvCqAFvjV3DeBnuw4YhDhV8KVZdKV9vq3Wo8c4XNmm3lLtF5rrYern5nD71NJ6vRYzR_fpiNhvNIJ4KFCJgmzAidG51oomgqjBlIEJSpvsm45InOIZfMZCajKTRP8EaDXCqW8QHnrIduf-7u6upzDz6sS-tP7SkH1d6vaUp5wiRhokFvftF9VoJZ72pbqvq4_uuMfQPGNXNU
CitedBy_id	crossref_primary_10_1016_j_cbpa_2022_102205 crossref_primary_10_1158_2159_8290_CD_17_1452 crossref_primary_10_7554_eLife_88836 crossref_primary_10_1039_D4MD00881B crossref_primary_10_1016_j_sbi_2018_07_007 crossref_primary_10_1002_minf_202400372 crossref_primary_10_1158_0008_5472_CAN_19_0729 crossref_primary_10_7554_eLife_94605 crossref_primary_10_3389_fonc_2023_1204829 crossref_primary_10_1016_j_pathol_2025_05_001 crossref_primary_10_1016_j_csbj_2021_06_007 crossref_primary_10_1080_14737140_2025_2451722 crossref_primary_10_1126_science_aao3048 crossref_primary_10_1016_j_esmoop_2025_105124 crossref_primary_10_1080_14622416_2024_2355859 crossref_primary_10_1158_1541_7786_MCR_17_0211 crossref_primary_10_1186_s12943_022_01676_9 crossref_primary_10_1177_1758835919895756 crossref_primary_10_1016_j_ccell_2015_08_006 crossref_primary_10_3389_fonc_2022_882940 crossref_primary_10_1038_s41375_025_02704_5 crossref_primary_10_1038_s41598_021_93107_w crossref_primary_10_1016_j_cels_2018_06_002 crossref_primary_10_1126_science_adp2742 crossref_primary_10_3390_ijms25105535 crossref_primary_10_1016_j_ccell_2017_12_004 crossref_primary_10_1038_s41388_017_0035_9 crossref_primary_10_1158_2159_8290_CD_20_0930 crossref_primary_10_1158_2643_3230_BCD_25_0099 crossref_primary_10_1016_j_humimm_2024_111221 crossref_primary_10_1016_j_gde_2022_101989 crossref_primary_10_1021_acsnano_5c09100 crossref_primary_10_1091_mbc_E21_11_0538 crossref_primary_10_7554_eLife_95481 crossref_primary_10_1002_pro_4125 crossref_primary_10_1158_2159_8290_CD_20_1351 crossref_primary_10_3390_cancers11081197 crossref_primary_10_1007_s40291_017_0299_3 crossref_primary_10_1016_j_molcel_2022_04_034 crossref_primary_10_1038_s41698_025_00821_z crossref_primary_10_3390_cancers14102379 crossref_primary_10_1007_s00761_017_0225_7 crossref_primary_10_1016_j_ejmech_2023_115231 crossref_primary_10_1371_journal_pone_0166583 crossref_primary_10_1158_2159_8290_CD_18_0784 crossref_primary_10_3390_cancers16162882 crossref_primary_10_1158_1078_0432_CCR_19_2004 crossref_primary_10_7717_peerj_14126 crossref_primary_10_1001_jamanetworkopen_2023_1476 crossref_primary_10_1007_s11910_023_01257_3 crossref_primary_10_1038_s41416_021_01679_1 crossref_primary_10_1016_j_ejca_2021_01_016 crossref_primary_10_1016_j_critrevonc_2022_103647 crossref_primary_10_1155_2018_9250757 crossref_primary_10_1158_1078_0432_CCR_23_1926 crossref_primary_10_2139_ssrn_3806797 crossref_primary_10_1186_s12935_020_1117_2 crossref_primary_10_1016_j_critrevonc_2024_104497 crossref_primary_10_1007_s00018_016_2155_8 crossref_primary_10_3390_app12157552 crossref_primary_10_1038_s41591_019_0612_2 crossref_primary_10_1038_s41388_018_0634_0 crossref_primary_10_3390_cancers14092110 crossref_primary_10_1038_s41379_021_00806_w crossref_primary_10_3389_fonc_2022_863043 crossref_primary_10_1007_s11912_019_0770_x crossref_primary_10_1016_j_ejmech_2025_117866 crossref_primary_10_7554_eLife_88836_3 crossref_primary_10_15252_msb_202210988 crossref_primary_10_1016_j_critrevonc_2022_103657 crossref_primary_10_1007_s11030_023_10699_3 crossref_primary_10_1093_oncolo_oyae113 crossref_primary_10_1073_pnas_2113491119 crossref_primary_10_1146_annurev_biochem_052521_040754 crossref_primary_10_3389_fimmu_2025_1598896 crossref_primary_10_1080_14737140_2019_1661778 crossref_primary_10_1038_nature17963 crossref_primary_10_1016_j_sbi_2021_07_005 crossref_primary_10_1038_s41392_021_00827_6 crossref_primary_10_1038_s41698_023_00359_y crossref_primary_10_1038_s41388_021_01834_1 crossref_primary_10_1016_j_cbi_2022_110056 crossref_primary_10_1038_bjc_2017_399 crossref_primary_10_1158_1078_0432_CCR_18_0836 crossref_primary_10_1038_onc_2017_276 crossref_primary_10_3390_cimb47070498 crossref_primary_10_1242_dmm_049229 crossref_primary_10_1038_nm_4369 crossref_primary_10_3390_biom12070905 crossref_primary_10_1007_s11864_022_00946_4 crossref_primary_10_3390_cancers12061532 crossref_primary_10_1016_j_talanta_2025_127997 crossref_primary_10_3389_fonc_2020_563407 crossref_primary_10_1007_s10637_021_01068_8 crossref_primary_10_1042_BST20170528 crossref_primary_10_1016_j_ejphar_2023_175752 crossref_primary_10_1007_s00280_017_3293_x crossref_primary_10_1016_j_cell_2016_12_015 crossref_primary_10_1097_SLA_0000000000004613 crossref_primary_10_1055_s_0043_1768029 crossref_primary_10_1186_s40478_018_0525_1 crossref_primary_10_3390_ph18081235 crossref_primary_10_1016_j_bpj_2024_06_028 crossref_primary_10_1186_s12885_022_09889_3 crossref_primary_10_1016_j_bbrc_2020_07_110 crossref_primary_10_1038_s41589_020_0609_7 crossref_primary_10_1038_s41698_025_00996_5 crossref_primary_10_3390_cancers14215306 crossref_primary_10_1002_1878_0261_13605 crossref_primary_10_1038_nature23291 crossref_primary_10_3390_cancers14082019 crossref_primary_10_1016_j_ctrv_2021_102335 crossref_primary_10_1016_j_physa_2025_130437 crossref_primary_10_1016_j_phrs_2025_107955 crossref_primary_10_1038_s41388_020_1263_y crossref_primary_10_1371_journal_pone_0217399 crossref_primary_10_1073_pnas_1610456113 crossref_primary_10_1158_2159_8290_CD_17_1263 crossref_primary_10_1080_14728222_2017_1311325 crossref_primary_10_1186_s12964_022_00917_0 crossref_primary_10_1158_0008_5472_CAN_21_3377 crossref_primary_10_1016_j_lfs_2025_123827 crossref_primary_10_1126_science_aau8059 crossref_primary_10_1007_s43538_021_00054_1 crossref_primary_10_1158_2159_8290_CD_18_0348 crossref_primary_10_1038_nrclinonc_2017_43 crossref_primary_10_1016_j_ejca_2021_02_036 crossref_primary_10_1021_jacs_0c11958 crossref_primary_10_1016_j_ijbiomac_2025_140475 crossref_primary_10_3390_pharmaceutics13091478 crossref_primary_10_1371_journal_pone_0163272 crossref_primary_10_1007_s00018_016_2297_8 crossref_primary_10_1038_s41388_021_01911_5 crossref_primary_10_1080_07391102_2025_2543358 crossref_primary_10_1016_j_coph_2021_02_009 crossref_primary_10_1016_j_critrevonc_2020_103008 crossref_primary_10_1016_j_lungcan_2019_01_007 crossref_primary_10_1002_slct_202400347 crossref_primary_10_1038_s41375_025_02526_5 crossref_primary_10_1042_BST20200485 crossref_primary_10_1016_j_prp_2024_155371 crossref_primary_10_1016_j_sbi_2020_09_007 crossref_primary_10_1158_2159_8290_CD_19_0356 crossref_primary_10_3390_molecules27238513 crossref_primary_10_3389_fbioe_2022_806851 crossref_primary_10_3389_fphar_2022_1019217 crossref_primary_10_1158_2159_8290_CD_17_1119 crossref_primary_10_1177_1758835921992974 crossref_primary_10_1158_2159_8290_CD_15_0896 crossref_primary_10_15252_msb_20177651 crossref_primary_10_1177_1535370220959657 crossref_primary_10_1158_2159_8290_CD_18_1321 crossref_primary_10_1073_pnas_1904529116 crossref_primary_10_1097_CAD_0000000000001537 crossref_primary_10_1038_s41576_021_00338_8 crossref_primary_10_1158_1541_7786_MCR_20_0687 crossref_primary_10_1111_neup_12846 crossref_primary_10_1158_1078_0432_CCR_23_3981 crossref_primary_10_3892_or_2025_8944 crossref_primary_10_1016_j_yexcr_2025_114440 crossref_primary_10_3390_cancers11010105 crossref_primary_10_1038_nm_4333 crossref_primary_10_1097_CMR_0000000000000854 crossref_primary_10_1002_gcc_22813 crossref_primary_10_1016_j_molcel_2016_10_029 crossref_primary_10_1084_jem_20192205 crossref_primary_10_3390_cancers12102936 crossref_primary_10_1016_j_sbi_2016_07_019 crossref_primary_10_3390_cancers16020445 crossref_primary_10_1038_s41467_019_10367_x crossref_primary_10_1111_pcmr_12932 crossref_primary_10_1039_C8TX00079D crossref_primary_10_3390_cancers13184639 crossref_primary_10_1007_s40265_019_01113_0 crossref_primary_10_1016_j_apsb_2024_02_018 crossref_primary_10_1093_oncolo_oyaf093 crossref_primary_10_1016_j_cllc_2020_02_018 crossref_primary_10_3389_fmed_2021_652005 crossref_primary_10_3390_cancers14174264 crossref_primary_10_15252_msb_20178077 crossref_primary_10_1016_j_jtho_2020_05_021 crossref_primary_10_3390_cancers15245805 crossref_primary_10_3390_cancers15041268 crossref_primary_10_1038_s41388_023_02829_w crossref_primary_10_1073_pnas_2407745121 crossref_primary_10_3390_cancers15184604 crossref_primary_10_1038_s41467_021_22125_z crossref_primary_10_1186_s12935_024_03280_x crossref_primary_10_3390_biom13081212 crossref_primary_10_1016_j_chembiol_2023_07_019 crossref_primary_10_3390_diagnostics11020252 crossref_primary_10_7554_eLife_95481_2 crossref_primary_10_1038_nrc_2017_79 crossref_primary_10_3390_ijms21031102 crossref_primary_10_1016_j_jtocrr_2022_100348 crossref_primary_10_1016_j_jss_2018_06_020 crossref_primary_10_1186_s12885_019_5864_1 crossref_primary_10_1186_s13045_022_01362_9 crossref_primary_10_3389_fcell_2016_00033 crossref_primary_10_1111_pcmr_12549 crossref_primary_10_3390_molecules26247561 crossref_primary_10_1016_j_esmogo_2024_100129 crossref_primary_10_1016_j_canlet_2024_216650 crossref_primary_10_1038_s41388_018_0171_x crossref_primary_10_1074_jbc_RA119_011536 crossref_primary_10_1634_theoncologist_2019_0223 crossref_primary_10_7554_eLife_60541 crossref_primary_10_3390_cancers13092201 crossref_primary_10_1111_cup_14704 crossref_primary_10_3389_fonc_2022_1067252 crossref_primary_10_1097_CMR_0000000000000997 crossref_primary_10_1002_cac2_12395 crossref_primary_10_1016_j_biopha_2022_113064 crossref_primary_10_1016_j_critrevonc_2020_103119 crossref_primary_10_3390_cancers12123511 crossref_primary_10_2147_LCTT_S493835 crossref_primary_10_1002_cbic_201900266 crossref_primary_10_1038_s41392_023_01441_4 crossref_primary_10_1038_s41467_020_18123_2 crossref_primary_10_1097_PAS_0000000000001155 crossref_primary_10_1016_j_yexcr_2020_112318 crossref_primary_10_1038_s41392_024_01760_0 crossref_primary_10_1177_17562848221110644 crossref_primary_10_3390_cancers13184650 crossref_primary_10_1001_jamanetworkopen_2020_35479 crossref_primary_10_1038_s41392_023_01705_z crossref_primary_10_1158_1541_7786_MCR_22_0626 crossref_primary_10_3390_cancers11060794 crossref_primary_10_2478_rrlm_2023_0018 crossref_primary_10_1042_BST20230558 crossref_primary_10_1093_annonc_mdy477 crossref_primary_10_1016_S1470_2045_16_30146_2 crossref_primary_10_1158_1078_0432_CCR_21_2138 crossref_primary_10_7554_eLife_94605_2 crossref_primary_10_1080_10799893_2025_2455594 crossref_primary_10_1097_CCO_0000000000000708 crossref_primary_10_1186_s13073_016_0366_0 crossref_primary_10_3390_genes12040553 crossref_primary_10_3390_cancers15194799 crossref_primary_10_1038_s41556_021_00654_5 crossref_primary_10_1038_bjc_2016_195 crossref_primary_10_1038_s41467_021_21159_7 crossref_primary_10_1038_s41591_018_0274_5 crossref_primary_10_1016_j_jtho_2023_07_024 crossref_primary_10_3389_fonc_2022_945620 crossref_primary_10_1371_journal_pone_0171512 crossref_primary_10_1016_j_str_2018_04_002 crossref_primary_10_1146_annurev_cancerbio_051320_124252 crossref_primary_10_3390_cells9010198 crossref_primary_10_3892_mmr_2018_8615 crossref_primary_10_1080_14737140_2020_1787156 crossref_primary_10_1038_s43018_020_0100_0 crossref_primary_10_1016_j_clcc_2024_04_004 crossref_primary_10_1200_EDBK_174934 crossref_primary_10_1038_s41556_018_0169_1 crossref_primary_10_1158_0008_5472_CAN_17_0768 crossref_primary_10_1200_PO_24_00266 crossref_primary_10_1038_s41571_023_00852_0 crossref_primary_10_1128_MCB_00132_17 crossref_primary_10_1158_0008_5472_CAN_19_1415 crossref_primary_10_1038_s42003_023_04519_5 crossref_primary_10_1128_JVI_01613_20 crossref_primary_10_1016_j_cels_2020_10_002 crossref_primary_10_1016_j_bioorg_2022_105597 crossref_primary_10_1016_j_jtho_2018_12_038 crossref_primary_10_1136_jcp_2023_209318 crossref_primary_10_3390_ijms23095158 crossref_primary_10_1038_s41419_022_04550_0 crossref_primary_10_1158_0008_5472_CAN_17_2033 crossref_primary_10_1177_1758834016670555 crossref_primary_10_1007_s11864_021_00901_9 crossref_primary_10_1146_annurev_cancerbio_061421_012927 crossref_primary_10_1016_j_ejphar_2024_177142 crossref_primary_10_1016_j_ajhg_2023_12_009 crossref_primary_10_1038_s43018_024_00817_x crossref_primary_10_1158_1078_0432_CCR_17_3384 crossref_primary_10_1158_2159_8290_CD_17_0682 crossref_primary_10_1038_nrd4778 crossref_primary_10_1038_s41467_021_21613_6 crossref_primary_10_1038_s41589_023_01454_8 crossref_primary_10_1111_1346_8138_17718 crossref_primary_10_1126_scisignal_adw3231 crossref_primary_10_1177_1758835919878013 crossref_primary_10_3390_ijms232315056 crossref_primary_10_1002_hed_27950 crossref_primary_10_1634_theoncologist_2017_0494 crossref_primary_10_3390_cancers16162796 crossref_primary_10_1016_j_jtho_2021_09_008 crossref_primary_10_3390_cancers11091262 crossref_primary_10_1016_j_semcancer_2019_11_007 crossref_primary_10_1038_s41388_019_1021_1 crossref_primary_10_1039_D1SC03444H crossref_primary_10_1530_EJE_21_0797 crossref_primary_10_1158_1078_0432_CCR_20_4189 crossref_primary_10_1158_1078_0432_CCR_20_2563 crossref_primary_10_1097_CCO_0000000000000817 crossref_primary_10_1093_oncolo_oyae297 crossref_primary_10_1186_s12918_018_0554_1 crossref_primary_10_1200_EDBK_321255 crossref_primary_10_3389_fonc_2022_1031378 crossref_primary_10_2174_0109298673258495231011065225 crossref_primary_10_1038_s41698_023_00467_9 crossref_primary_10_1002_ctm2_1764 crossref_primary_10_1111_cas_15401 crossref_primary_10_1002_ijc_32320 crossref_primary_10_1158_1078_0432_CCR_23_1393 crossref_primary_10_1016_j_ccell_2016_06_024 crossref_primary_10_3390_cancers11101480 crossref_primary_10_1038_s41568_023_00650_x crossref_primary_10_1158_1078_0432_CCR_19_0422 crossref_primary_10_1136_bcr_2017_219720 crossref_primary_10_1136_gutjnl_2016_312986 crossref_primary_10_1016_j_ctrv_2018_04_006 crossref_primary_10_1002_onco_13795 crossref_primary_10_1007_s12326_017_0248_2 crossref_primary_10_62347_MVNL2093 crossref_primary_10_1016_j_ctrv_2025_102905 crossref_primary_10_1038_s41586_019_1730_1 crossref_primary_10_3389_fimmu_2024_1366260 crossref_primary_10_1038_s41388_019_0866_7 crossref_primary_10_4103_jcrt_jcrt_1504_23 crossref_primary_10_1002_1878_0261_12698 crossref_primary_10_3390_ijms24109073 crossref_primary_10_1016_j_ccell_2016_02_010 crossref_primary_10_1016_j_isci_2023_108480 crossref_primary_10_1007_s00381_025_06799_0 crossref_primary_10_3390_ijms25094633 crossref_primary_10_1038_nrc_2017_84 crossref_primary_10_1007_s12022_021_09698_7 crossref_primary_10_1158_0008_5472_CAN_19_0244 crossref_primary_10_1158_2159_8290_CD_24_0024 crossref_primary_10_3389_fcell_2021_696558 crossref_primary_10_1002_cam4_3103 crossref_primary_10_1038_s41467_022_31430_0 crossref_primary_10_1007_s00280_023_04544_5 crossref_primary_10_1038_s41467_017_01274_0 crossref_primary_10_1158_1078_0432_CCR_18_2062 crossref_primary_10_1158_2159_8290_CD_23_0280 crossref_primary_10_1016_j_humpath_2025_105882 crossref_primary_10_3390_cancers11121972 crossref_primary_10_1016_j_amolm_2025_100073 crossref_primary_10_1093_neuonc_now261
ContentType	Journal Article
Copyright	Copyright © 2015 Elsevier Inc. All rights reserved.
Copyright_xml	– notice: Copyright © 2015 Elsevier Inc. All rights reserved.
DBID	CGR CUY CVF ECM EIF NPM 7X8
DOI	10.1016/j.ccell.2015.08.001
DatabaseName	Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed MEDLINE - Academic
DatabaseTitle	MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) MEDLINE - Academic
DatabaseTitleList	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: 7X8 name: MEDLINE - Academic url: https://search.proquest.com/medline sourceTypes: Aggregation Database
DeliveryMethod	no_fulltext_linktorsrc
Discipline	Medicine
EISSN	1878-3686
ExternalDocumentID	26343582
Genre	Research Support, Non-U.S. Gov't Journal Article Research Support, N.I.H., Extramural
GrantInformation_xml	– fundername: NCI NIH HHS grantid: P01CA129243 – fundername: NCI NIH HHS grantid: T32 CA062948 – fundername: NCI NIH HHS grantid: R01 CA169351 – fundername: NCI NIH HHS grantid: P01 CA129243 – fundername: NCI NIH HHS grantid: P30 CA008748 – fundername: NCI NIH HHS grantid: R01CA169351
GroupedDBID	--- --K 0R~ 0SF 1~5 29B 2WC 4.4 457 4G. 53G 5GY 62- 6I. 6J9 7-5 AACTN AAEDT AAEDW AAFTH AAKRW AAKUH AALRI AAMRU AAVLU AAXUO ABJNI ABMAC ABVKL ACGFO ACGFS ADBBV ADEZE ADVLN AEFWE AENEX AEXQZ AFTJW AGHFR AGKMS AITUG AKAPO AKRWK ALMA_UNASSIGNED_HOLDINGS AMRAJ ASPBG AVWKF AZFZN BAWUL CGR CS3 CUY CVF DIK DU5 E3Z EBS ECM EIF EJD F5P FCP FDB FEDTE FIRID HVGLF IH2 IHE IXB J1W JIG M3Z M41 NCXOZ NPM O-L O9- OK1 P2P RCE RIG ROL RPZ SES SSZ TR2 UDS 7X8 AAFWJ AAYWO ABDGV ACVFH ADCNI AEUPX AFPUW AIGII AKBMS AKYEP APXCP EFKBS
ID	FETCH-LOGICAL-c562t-e2c02d6cfdc5c0a176dd98e612a4db3835cfef82dbdb17eade33339f8a2b39332
IEDL.DBID	7X8
ISICitedReferencesCount	417
ISICitedReferencesURI	http://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestLinkType=CitingArticles&DestApp=WOS_CPL&KeyUT=000361420900014&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D
ISSN	1878-3686
IngestDate	Thu Oct 02 05:49:24 EDT 2025 Thu Jan 02 23:04:09 EST 2025
IsDoiOpenAccess	false
IsOpenAccess	true
IsPeerReviewed	true
IsScholarly	true
Issue	3
Language	English
License	Copyright © 2015 Elsevier Inc. All rights reserved.
LinkModel	DirectLink
MergedId	FETCHMERGED-LOGICAL-c562t-e2c02d6cfdc5c0a176dd98e612a4db3835cfef82dbdb17eade33339f8a2b39332
Notes	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
OpenAccessLink	https://dx.doi.org/10.1016/j.ccell.2015.08.001
PMID	26343582
PQID	1713528026
PQPubID	23479
ParticipantIDs	proquest_miscellaneous_1713528026 pubmed_primary_26343582
PublicationCentury	2000
PublicationDate	2015-09-14
PublicationDateYYYYMMDD	2015-09-14
PublicationDate_xml	– month: 09 year: 2015 text: 2015-09-14 day: 14
PublicationDecade	2010
PublicationPlace	United States
PublicationPlace_xml	– name: United States
PublicationTitle	Cancer cell
PublicationTitleAlternate	Cancer Cell
PublicationYear	2015
References	26373275 - Cancer Cell. 2015 Sep 14;28(3):279-81
References_xml	– reference: 26373275 - Cancer Cell. 2015 Sep 14;28(3):279-81
SSID	ssj0016179
Score	2.6337445
Snippet	ERK signaling requires RAS-induced RAF dimerization and is limited by feedback. Activated BRAF mutants evade feedback inhibition of RAS by either of two...
SourceID	proquest pubmed
SourceType	Aggregation Database Index Database
StartPage	370
SubjectTerms	Cell Line, Tumor Dimerization Drug Resistance, Neoplasm - drug effects Drug Resistance, Neoplasm - genetics Humans MAP Kinase Signaling System - drug effects MAP Kinase Signaling System - genetics Mutation - genetics Protein Kinase Inhibitors - pharmacology Proto-Oncogene Proteins B-raf - antagonists & inhibitors Proto-Oncogene Proteins B-raf - genetics ras Proteins - genetics
Title	BRAF Mutants Evade ERK-Dependent Feedback by Different Mechanisms that Determine Their Sensitivity to Pharmacologic Inhibition
URI	https://www.ncbi.nlm.nih.gov/pubmed/26343582 https://www.proquest.com/docview/1713528026
Volume	28
WOSCitedRecordID	wos000361420900014&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D
hasFullText
inHoldings	1
isFullTextHit
isPrint
link	http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwpV1LS8NAEF7Uinjx_agvVvAaTHY3yeYk1RoUaSm1Qm9lX6FFTKtJBS_-dneSLT0JgjnkFgg7szPf7nwzH0JXoaKhCDXzlGaRxwT1PcEMtcEwY1RHRBAmKrGJuNvlw2HScxduhaNVLmJiFaj1VMEd-XUAWnKE2yPDzezdA9UoqK46CY1V1KAWyoBXx8NlFcFmZ4C_AQcKQMSjxdShit-l4GYcuF1hNcPTD37HmFWuSbf_-5c7aMuhTNyq3WIXrZh8D210XB19H33f9lsp7sxBQrjAFk1rg-_7T17bSeKWOLVZTQr1iuUXbjsRlRJ3DDQKT4q3ApdjUeK2I9MYPICCA34GOnytR4HLKe4t52JPFH7MxxNZMcQO0Et6P7h78JwSg6csPio9Q5RPdKQyrULliyCOtE64sehIMC3tITdUmck40VLLIAYONrVPknFBJE0oJYdoLZ_m5hhhoQIZZ34sYuhM8YXIOJUJV1ITaoyiTXS5WNmR9XQwksjNdF6MlmvbREe1eUazeiTHiESUQc_vyR--PkWbYHUgfQTsDDUyu8_NOVpXn-Wk-LioXMi-u73ODz8c0sI
linkProvider	ProQuest
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=BRAF+Mutants+Evade+ERK-Dependent+Feedback+by+Different+Mechanisms+that+Determine+Their+Sensitivity+to+Pharmacologic+Inhibition&rft.jtitle=Cancer+cell&rft.au=Yao%2C+Zhan&rft.au=Torres%2C+Neilawattie+M&rft.au=Tao%2C+Anthony&rft.au=Gao%2C+Yijun&rft.date=2015-09-14&rft.issn=1878-3686&rft.eissn=1878-3686&rft.volume=28&rft.issue=3&rft.spage=370&rft_id=info:doi/10.1016%2Fj.ccell.2015.08.001&rft.externalDBID=NO_FULL_TEXT
thumbnail_l	http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1878-3686&client=summon
thumbnail_m	http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1878-3686&client=summon
thumbnail_s	http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1878-3686&client=summon