Targeting MTAP increases PARP inhibitor susceptibility in triple-negative breast cancer through a feed-forward loop
Triple-negative breast cancer (TNBC) represents the most malignant subtype of breast cancer. The clinical application of PARP inhibitors (PARPi) is limited by the low frequency of BRCA1/2 mutations in TNBC. Here, we identified that MTAP deletion sensitized genotoxic agents in our clinical cohort of...
Uloženo v:
| Vydáno v: | The Journal of clinical investigation Ročník 135; číslo 13; s. 1 - 18 |
|---|---|
| Hlavní autoři: | , , , , , , , , , , , , , , |
| Médium: | Journal Article |
| Jazyk: | angličtina |
| Vydáno: |
United States
American Society for Clinical Investigation
01.07.2025
|
| Témata: | |
| ISSN: | 1558-8238, 0021-9738, 1558-8238 |
| On-line přístup: | Získat plný text |
| Tagy: |
Přidat tag
Žádné tagy, Buďte první, kdo vytvoří štítek k tomuto záznamu!
|
| Abstract | Triple-negative breast cancer (TNBC) represents the most malignant subtype of breast cancer. The clinical application of PARP inhibitors (PARPi) is limited by the low frequency of BRCA1/2 mutations in TNBC. Here, we identified that MTAP deletion sensitized genotoxic agents in our clinical cohort of metastatic TNBC. Further study demonstrated that MTAP deficiency or inhibition rendered TNBC susceptibility to chemotherapeutic agents, particularly PARPi. Mechanistically, targeting MTAP that synergized with PARPi by disrupting the METTL16-MAT2A axis involved in methionine metabolism and depleting in vivo s-adenosylmethionine (SAM) levels. Exhausted SAM in turn impaired PARPi-induced DNA damage repair through attenuation of MRE11 recruitment and end resection by diminishing MRE11 methylation. Notably, brain metastatic TNBC markedly benefited from a lower dose of PARPi and MTAP deficiency/inhibition synergy due to the inherently limited methionine environment in the brain. Collectively, our findings revealed a feed-forward loop between methionine metabolism and DNA repair through SAM, highlighting a therapeutic strategy of PARPi combined with MTAP deficiency/inhibition for TNBC. |
|---|---|
| AbstractList | Triple-negative breast cancer (TNBC) represents the most malignant subtype of breast cancer. The clinical application of PARP inhibitors (PARPi) is limited by the low frequency of BRCA1/2 mutations in TNBC. Here, we identified that MTAP deletion sensitized genotoxic agents in our clinical cohort of metastatic TNBC. Further study demonstrated that MTAP deficiency or inhibition rendered TNBC susceptibility to chemotherapeutic agents, particularly PARPi. Mechanistically, targeting MTAP that synergized with PARPi by disrupting the METTL16-MAT2A axis involved in methionine metabolism and depleting in vivo s-adenosylmethionine (SAM) levels. Exhausted SAM in turn impaired PARPi-induced DNA damage repair through attenuation of MRE11 recruitment and end resection by diminishing MRE11 methylation. Notably, brain metastatic TNBC markedly benefited from a lower dose of PARPi and MTAP deficiency/inhibition synergy due to the inherently limited methionine environment in the brain. Collectively, our findings revealed a feed-forward loop between methionine metabolism and DNA repair through SAM, highlighting a therapeutic strategy of PARPi combined with MTAP deficiency/inhibition for TNBC. Triple-negative breast cancer (TNBC) represents the most malignant subtype of breast cancer. The clinical application of PARP inhibitors (PARPi) is limited by the low frequency of BRCA1/2 mutations in TNBC. Here, we identified that MTAP deletion sensitized genotoxic agents in our clinical cohort of metastatic TNBC. Further study demonstrated that MTAP deficiency or inhibition rendered TNBC susceptibility to chemotherapeutic agents, particularly PARPi. Mechanistically, targeting MTAP that synergized with PARPi by disrupting the METTL16-MAT2A axis involved in methionine metabolism and depleting in vivo s-adenosylmethionine (SAM) levels. Exhausted SAM in turn impaired PARPi-induced DNA damage repair through attenuation of MRE11 recruitment and end resection by diminishing MRE11 methylation. Notably, brain metastatic TNBC markedly benefited from a lower dose of PARPi and MTAP deficiency/inhibition synergy due to the inherently limited methionine environment in the brain. Collectively, our findings revealed a feed-forward loop between methionine metabolism and DNA repair through SAM, highlighting a therapeutic strategy of PARPi combined with MTAP deficiency/inhibition for TNBC.Triple-negative breast cancer (TNBC) represents the most malignant subtype of breast cancer. The clinical application of PARP inhibitors (PARPi) is limited by the low frequency of BRCA1/2 mutations in TNBC. Here, we identified that MTAP deletion sensitized genotoxic agents in our clinical cohort of metastatic TNBC. Further study demonstrated that MTAP deficiency or inhibition rendered TNBC susceptibility to chemotherapeutic agents, particularly PARPi. Mechanistically, targeting MTAP that synergized with PARPi by disrupting the METTL16-MAT2A axis involved in methionine metabolism and depleting in vivo s-adenosylmethionine (SAM) levels. Exhausted SAM in turn impaired PARPi-induced DNA damage repair through attenuation of MRE11 recruitment and end resection by diminishing MRE11 methylation. Notably, brain metastatic TNBC markedly benefited from a lower dose of PARPi and MTAP deficiency/inhibition synergy due to the inherently limited methionine environment in the brain. Collectively, our findings revealed a feed-forward loop between methionine metabolism and DNA repair through SAM, highlighting a therapeutic strategy of PARPi combined with MTAP deficiency/inhibition for TNBC. Triple-negative breast cancer (TNBC) represents the most malignant subtype of breast cancer. The clinical application of PARP inhibitors (PARPi) is limited by the low frequency of BRCA1/2 mutations in TNBC. Here, we identified that MTAP deletion sensitized genotoxic agents in our clinical cohort of metastatic TNBC. Further study demonstrated that MTAP deficiency or inhibition rendered TNBC susceptibility to chemotherapeutic agents, particularly PARPi. Mechanistically, targeting MTAP that synergized with PARPi by disrupting the METTL16-MAT2A axis involved in methionine metabolism and depleting in vivo s-adenosylmethionine (SAM) levels. Exhausted SAM in turn impaired PARPi-induced DNA damage repair through attenuation of MRE11 recruitment and end resection by diminishing MRE11 methylation. Notably, brain metastatic TNBC markedly benefited from a lower dose of PARPi and MTAP deficiency/inhibition synergy due to the inherently limited methionine environment in the brain. Collectively, our findings revealed a feed-forward loop between methionine metabolism and DNA repair through SAM, highlighting a therapeutic strategy of PARPi combined with MTAP deficiency/inhibition for TNBC. Targeting MTAP confers TNBC to PARP inhibitors |
| Audience | Academic |
| Author | Yang, Wen Zhang, Lingxin Wu, Zheming Tao, Kaixiong Weinshilboum, Richard M. Wang, Liewei Tu, Xinyi Hou, Jing Lou, Zhenkun Zeng, Xiangyu Zhao, Fei Jiang, Qi Zhu, Shouhai Hao, Yalan Zhang, Yong |
| AuthorAffiliation | 1 Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China 4 Department of Radiation Oncology, Hubei Cancer Hospital, Tongji Medical College, and 5 Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China 7 Analytical Instrumentation Center, Hunan University, Changsha, China 2 College of Biology, Hunan University, Changsha, China 3 Department of Oncology, Mayo Clinic, Rochester, Minnesota, USA 8 Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota, USA 6 Department of Breast Surgery, Guizhou Provincial People’s Hospital, Guiyang, China |
| AuthorAffiliation_xml | – name: 1 Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China – name: 3 Department of Oncology, Mayo Clinic, Rochester, Minnesota, USA – name: 2 College of Biology, Hunan University, Changsha, China – name: 6 Department of Breast Surgery, Guizhou Provincial People’s Hospital, Guiyang, China – name: 5 Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China – name: 4 Department of Radiation Oncology, Hubei Cancer Hospital, Tongji Medical College, and – name: 8 Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota, USA – name: 7 Analytical Instrumentation Center, Hunan University, Changsha, China |
| Author_xml | – sequence: 1 givenname: Xiangyu surname: Zeng fullname: Zeng, Xiangyu – sequence: 2 givenname: Fei surname: Zhao fullname: Zhao, Fei – sequence: 3 givenname: Xinyi surname: Tu fullname: Tu, Xinyi – sequence: 4 givenname: Yong surname: Zhang fullname: Zhang, Yong – sequence: 5 givenname: Wen surname: Yang fullname: Yang, Wen – sequence: 6 givenname: Jing surname: Hou fullname: Hou, Jing – sequence: 7 givenname: Qi surname: Jiang fullname: Jiang, Qi – sequence: 8 givenname: Shouhai surname: Zhu fullname: Zhu, Shouhai – sequence: 9 givenname: Zheming surname: Wu fullname: Wu, Zheming – sequence: 10 givenname: Yalan surname: Hao fullname: Hao, Yalan – sequence: 11 givenname: Lingxin orcidid: 0000-0001-7068-7168 surname: Zhang fullname: Zhang, Lingxin – sequence: 12 givenname: Richard M. surname: Weinshilboum fullname: Weinshilboum, Richard M. – sequence: 13 givenname: Kaixiong surname: Tao fullname: Tao, Kaixiong – sequence: 14 givenname: Liewei surname: Wang fullname: Wang, Liewei – sequence: 15 givenname: Zhenkun surname: Lou fullname: Lou, Zhenkun |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/40590219$$D View this record in MEDLINE/PubMed |
| BookMark | eNqNk8tu1DAUhiNURC-w4AVQJCQEi7S2EyfOqhpVXAYVtSoDW-vEOcm4ytiD7RT69jj0NgNdsPLt-3-fi72f7BhrMEleUnJIacWOPp_MqRCUkSfJHuVcZILlYmdjvpvse39JCC0KXjxLdgvCa8JovZf4BbgegzZ9-mUxO0-1UQ7Bo0_PZxfTcqkbHaxL_egVrkNcDTpcx4M0OL0eMDPYQ9BXmDaTMKQKjEKXhqWzY79MIe0Q26yz7ie4Nh2sXT9PnnYweHxxOx4k3z68X5x8yk7PPs5PZqeZKqsyZIVQlFdcASABpgqoeQ2CNjWoVvC2ZCRnXS0Kypq6zpGxumoYipqAgjaK8oNkfuPbWriUa6dX4K6lBS3_bFjXS3BBqwElkBKhq5oqjgWpBAB0tOGUsJwXqi2i1_GN13psVtgqNMHBsGW6fWL0Uvb2SlLGiOB8cnh76-DsjxF9kCsdSzoMYNCOXuaMlXm8sZrQ13-hl3Z0JtYqUnnsW1kz_kD1EDPQprPxYjWZypkoalaWnJBIZY9QPRqMUcZn1Om4vcUfPsJPJcWVVo8K3m0JIhPwV-hh9F7Ov178P3v2fZt9s8EuEYaw9HYYg7bGb4OvNltz35O7Rx6BoxtAOeu9w04qHWDyianpQVIip28k77_RQ5z3ijvTf9nfEQgYRw |
| CitedBy_id | crossref_primary_10_1038_s41598_025_13361_0 crossref_primary_10_1172_JCI193171 |
| Cites_doi | 10.1038/cr.2011.128 10.1038/s41571-021-00565-2 10.6004/jnccn.2024.0035 10.1038/s43018-022-00429-3 10.1126/science.aam7344 10.1038/nature21671 10.1158/1078-0432.CCR-13-3446 10.1016/j.molcel.2018.07.025 10.1016/j.ccell.2020.12.010 10.1172/JCI81749 10.1126/sciadv.aaz3221 10.1158/2159-8290.CD-23-0669 10.1200/JCO.22.01239 10.1016/j.cell.2021.12.005 10.1016/j.molcel.2018.08.004 10.1074/jbc.M110.198374 10.1016/j.semcancer.2022.03.008 10.1056/NEJMoa1706450 10.1038/nature25432 10.1038/s41586-019-1437-3 10.1016/j.tcb.2015.07.009 10.1016/j.cmet.2021.12.001 10.1007/978-1-4939-2522-3_5 10.1126/scitranslmed.abn7571 10.1126/science.aad5214 10.1038/s41467-021-26413-6 10.1016/j.tcb.2019.11.005 10.1016/j.jbc.2023.105492 10.1126/sciadv.add8928 10.1126/scitranslmed.aal2463 10.1056/NEJMoa1802905 10.1093/bib/bbab260 10.1016/j.cell.2021.01.048 10.1158/1078-0432.CCR-21-0361 10.1007/978-1-0716-0868-5_20 10.4161/cc.4.7.1830 10.1038/nsmb.1568 10.1158/2159-8290.CD-19-0270 10.1038/s41556-021-00723-9 10.1038/nm.4292 10.1128/MCB.02025-07 10.1158/2159-8290.CD-19-1228 10.1200/JCO.2007.14.4147 10.1016/j.cell.2023.11.022 10.1016/j.cmet.2020.01.006 10.1136/bmj-2022-071674 10.1021/acs.jmedchem.1c00067 10.1038/s41467-021-27559-z 10.1016/j.celrep.2016.03.043 10.1016/j.cmet.2014.03.017 10.1007/978-1-0716-0904-0_5 10.1038/s41571-020-00452-2 10.1016/j.cell.2018.11.024 10.1016/j.annonc.2021.09.019 10.1074/jbc.M702287200 10.1016/j.ccell.2019.05.014 10.1016/j.cell.2017.05.003 10.1016/j.apsb.2022.03.026 10.1021/acs.jmedchem.0c01895 10.1172/JCI177357 10.1038/nrm.2017.48 10.1126/science.aad5944 |
| ContentType | Journal Article |
| Copyright | COPYRIGHT 2025 American Society for Clinical Investigation Copyright American Society for Clinical Investigation 2025 2025 Zeng et al. 2025 Zeng et al. |
| Copyright_xml | – notice: COPYRIGHT 2025 American Society for Clinical Investigation – notice: Copyright American Society for Clinical Investigation 2025 – notice: 2025 Zeng et al. 2025 Zeng et al. |
| DBID | AAYXX CITATION CGR CUY CVF ECM EIF NPM IOV ISR 3V. 7RV 7X7 7XB 88A 88E 8AO 8FE 8FH 8FI 8FJ 8FK ABUWG AFKRA AZQEC BBNVY BEC BENPR BHPHI CCPQU DWQXO FYUFA GHDGH GNUQQ HCIFZ K9. KB0 LK8 M0S M1P M7P NAPCQ PHGZM PHGZT PJZUB PKEHL PPXIY PQEST PQGLB PQQKQ PQUKI PRINS S0X 7X8 5PM DOA |
| DOI | 10.1172/JCI188120 |
| DatabaseName | CrossRef Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed Gale In Context: Opposing Viewpoints Gale In Context: Science ProQuest Central (Corporate) Nursing & Allied Health Database Health & Medical Collection ProQuest Central (purchase pre-March 2016) Biology Database (Alumni Edition) Medical Database (Alumni Edition) ProQuest Pharma Collection ProQuest SciTech Collection ProQuest Natural Science Collection ProQuest Hospital Collection Hospital Premium Collection (Alumni Edition) ProQuest Central (Alumni) (purchase pre-March 2016) ProQuest Central (Alumni) ProQuest Central UK/Ireland ProQuest Central Essentials Biological Science Collection eLibrary ProQuest Central Natural Science Collection ProQuest One ProQuest Central Health Research Premium Collection Health Research Premium Collection (Alumni) ProQuest Central Student SciTech Premium Collection ProQuest Health & Medical Complete (Alumni) Nursing & Allied Health Database (Alumni Edition) Biological Sciences Health & Medical Collection (Alumni) Medical Database Biological Science Database ProQuest Nursing and Allied Health Premium ProQuest Central Premium ProQuest One Academic ProQuest Health & Medical Research Collection ProQuest One Academic Middle East (New) One Health & Nursing ProQuest One Academic Eastern Edition (DO NOT USE) ProQuest One Applied & Life Sciences ProQuest One Academic (retired) ProQuest One Academic UKI Edition ProQuest Central China SIRS Editorial MEDLINE - Academic PubMed Central (Full Participant titles) DOAJ Directory of Open Access Journals |
| DatabaseTitle | CrossRef MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) ProQuest Central Student ProQuest One Academic Middle East (New) ProQuest Central Essentials SIRS Editorial elibrary ProQuest Health & Medical Complete (Alumni) ProQuest Central (Alumni Edition) SciTech Premium Collection ProQuest One Community College ProQuest One Health & Nursing ProQuest Natural Science Collection ProQuest Pharma Collection ProQuest Central China ProQuest Biology Journals (Alumni Edition) ProQuest Central ProQuest One Applied & Life Sciences ProQuest Health & Medical Research Collection Health Research Premium Collection Health and Medicine Complete (Alumni Edition) Natural Science Collection ProQuest Central Korea Health & Medical Research Collection Biological Science Collection ProQuest Central (New) ProQuest Medical Library (Alumni) ProQuest Biological Science Collection ProQuest One Academic Eastern Edition ProQuest Nursing & Allied Health Source ProQuest Hospital Collection Health Research Premium Collection (Alumni) Biological Science Database ProQuest SciTech Collection 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 | MEDLINE - Academic ProQuest Central Student MEDLINE |
| Database_xml | – sequence: 1 dbid: DOA name: Directory of Open Access Journals url: https://www.doaj.org/ sourceTypes: Open Website – sequence: 2 dbid: NPM name: PubMed url: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 3 dbid: 7RV name: Nursing & Allied Health Database url: https://search.proquest.com/nahs sourceTypes: Aggregation Database |
| DeliveryMethod | fulltext_linktorsrc |
| Discipline | Medicine |
| EISSN | 1558-8238 |
| EndPage | 18 |
| ExternalDocumentID | oai_doaj_org_article_a06eaf7b706e4078aaaf1b5102354cd4 PMC12208554 A849266500 40590219 10_1172_JCI188120 |
| Genre | Journal Article |
| GeographicLocations | China |
| GeographicLocations_xml | – name: China |
| GrantInformation_xml | – fundername: the Special Research Fund of the Wuhan Knowledge Innovation Program grantid: 2023020201010176 – fundername: the National Natural Science Foundation of China grantid: 82303827,82373123,32370779,82260502,82272656 – fundername: the Provincial Natural Science Foundation of Hunan grantid: 2024JJ3008 |
| GroupedDBID | --- -~X .55 .XZ 08G 08P 29K 354 36B 5GY 5RE 5RS 7RV 7X7 88E 8AO 8F7 8FE 8FH 8FI 8FJ 8R4 8R5 AAWTL AAYXX ABOCM ABPMR ABUWG ACGFO ACIHN ACNCT ACPRK ADBBV ADPDF AEAQA AENEX AFCHL AFFHD AFKRA AHMBA ALMA_UNASSIGNED_HOLDINGS AOIJS ASPBG AVWKF AZFZN BAWUL BBNVY BCU BEC BENPR BHPHI BKEYQ BLC BPHCQ BVXVI CCPQU CITATION CS3 D-I DIK DU5 E3Z EBS EJD EMB EX3 F5P FRP FYUFA GROUPED_DOAJ GX1 HCIFZ HMCUK IAO IEA IHR IHW INH IOF IOV IPO ISR ITC KQ8 L7B LK8 M1P M5~ M7P NAPCQ OBH OCB ODZKP OFXIZ OGEVE OHH OK1 OVD OVIDX OVT P2P P6G PHGZM PHGZT PJZUB PPXIY PQGLB PQQKQ PROAC PSQYO Q2X RPM S0X SJFOW SV3 TEORI TR2 TVE UKHRP VVN W2D WH7 WOQ WOW X7M XSB YFH YHG YKV YOC ZY1 ~H1 ALIPV CGR CUY CVF ECM EIF NPM 3V. 7XB 88A 8FK AZQEC DWQXO GNUQQ K9. PKEHL PQEST PQUKI PRINS 7X8 PUEGO 5PM |
| ID | FETCH-LOGICAL-c676t-48c1575caae0a2c4a959a81b9acd85d62032f98412b993e2297b2e890acadaae3 |
| IEDL.DBID | DOA |
| ISICitedReferencesCount | 2 |
| ISICitedReferencesURI | http://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestLinkType=CitingArticles&DestApp=WOS_CPL&KeyUT=001530480600023&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D |
| ISSN | 1558-8238 0021-9738 |
| IngestDate | Fri Oct 03 12:53:05 EDT 2025 Tue Nov 04 02:04:50 EST 2025 Tue Aug 26 08:59:43 EDT 2025 Tue Oct 07 05:13:09 EDT 2025 Sat Nov 29 13:46:59 EST 2025 Sat Nov 29 11:50:59 EST 2025 Sat Nov 29 10:28:58 EST 2025 Wed Nov 26 10:45:06 EST 2025 Wed Nov 26 10:45:09 EST 2025 Tue Aug 12 02:17:42 EDT 2025 Mon Jul 21 06:03:36 EDT 2025 Tue Nov 18 21:38:16 EST 2025 Sat Nov 29 07:45:20 EST 2025 |
| IsDoiOpenAccess | true |
| IsOpenAccess | true |
| IsPeerReviewed | true |
| IsScholarly | true |
| Issue | 13 |
| Keywords | Oncology Breast cancer Amino acid metabolism DNA repair Therapeutics |
| Language | English |
| License | http://creativecommons.org/licenses/by/4.0 This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
| LinkModel | DirectLink |
| MergedId | FETCHMERGED-LOGICAL-c676t-48c1575caae0a2c4a959a81b9acd85d62032f98412b993e2297b2e890acadaae3 |
| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 Authorship note: XZ and FZ contributed equally to this work and are co–first authors. |
| ORCID | 0000-0001-7068-7168 |
| OpenAccessLink | https://doaj.org/article/a06eaf7b706e4078aaaf1b5102354cd4 |
| PMID | 40590219 |
| PQID | 3232196925 |
| PQPubID | 42166 |
| PageCount | 18 |
| ParticipantIDs | doaj_primary_oai_doaj_org_article_a06eaf7b706e4078aaaf1b5102354cd4 pubmedcentral_primary_oai_pubmedcentral_nih_gov_12208554 proquest_miscellaneous_3226351074 proquest_journals_3232196925 gale_infotracmisc_A849266500 gale_infotracgeneralonefile_A849266500 gale_infotracacademiconefile_A849266500 gale_incontextgauss_ISR_A849266500 gale_incontextgauss_IOV_A849266500 gale_healthsolutions_A849266500 pubmed_primary_40590219 crossref_citationtrail_10_1172_JCI188120 crossref_primary_10_1172_JCI188120 |
| PublicationCentury | 2000 |
| PublicationDate | 2025-07-01 |
| PublicationDateYYYYMMDD | 2025-07-01 |
| PublicationDate_xml | – month: 07 year: 2025 text: 2025-07-01 day: 01 |
| PublicationDecade | 2020 |
| PublicationPlace | United States |
| PublicationPlace_xml | – name: United States – name: Ann Arbor |
| PublicationTitle | The Journal of clinical investigation |
| PublicationTitleAlternate | J Clin Invest |
| PublicationYear | 2025 |
| Publisher | American Society for Clinical Investigation |
| Publisher_xml | – name: American Society for Clinical Investigation |
| References | B20 B64 B21 B22 B23 B24 B25 B26 B27 B28 B29 B30 B31 B32 B33 B34 B35 B36 B37 B38 B39 B1 B2 B3 B4 B5 B6 B7 B8 B9 B40 B41 B42 B43 B44 B45 B46 B47 B48 B49 B50 B51 B52 B53 B10 B11 Tan (B54) 1999; 5 B12 B56 B13 B57 B14 B58 B15 B59 B16 B17 B18 B19 Kokkinakis (B55) 2001; 61 B60 B61 B62 B63 |
| References_xml | – ident: B42 doi: 10.1038/cr.2011.128 – ident: B3 doi: 10.1038/s41571-021-00565-2 – ident: B27 doi: 10.6004/jnccn.2024.0035 – ident: B35 doi: 10.1038/s43018-022-00429-3 – volume: 5 start-page: 2157 issue: 8 year: 1999 ident: B54 article-title: Efficacy of recombinant methioninase in combination with cisplatin on human colon tumors in nude mice publication-title: Clin Cancer Res – volume: 61 start-page: 4017 issue: 10 year: 2001 ident: B55 article-title: Synergy between methionine stress and chemotherapy in the treatment of brain tumor xenografts in athymic mice publication-title: Cancer Res – ident: B17 doi: 10.1126/science.aam7344 – ident: B38 doi: 10.1038/nature21671 – ident: B50 doi: 10.1158/1078-0432.CCR-13-3446 – ident: B33 doi: 10.1016/j.molcel.2018.07.025 – ident: B12 doi: 10.1016/j.ccell.2020.12.010 – ident: B52 doi: 10.1172/JCI81749 – ident: B51 doi: 10.1126/sciadv.aaz3221 – ident: B31 doi: 10.1158/2159-8290.CD-23-0669 – ident: B20 doi: 10.1200/JCO.22.01239 – ident: B23 doi: 10.1016/j.cell.2021.12.005 – ident: B34 doi: 10.1016/j.molcel.2018.08.004 – ident: B36 doi: 10.1074/jbc.M110.198374 – ident: B5 doi: 10.1016/j.semcancer.2022.03.008 – ident: B18 doi: 10.1056/NEJMoa1706450 – ident: B64 doi: 10.1038/nature25432 – ident: B46 doi: 10.1038/s41586-019-1437-3 – ident: B60 doi: 10.1016/j.tcb.2015.07.009 – ident: B48 doi: 10.1016/j.cmet.2021.12.001 – ident: B41 doi: 10.1007/978-1-4939-2522-3_5 – ident: B25 doi: 10.1126/scitranslmed.abn7571 – ident: B10 doi: 10.1126/science.aad5214 – ident: B39 doi: 10.1038/s41467-021-26413-6 – ident: B56 doi: 10.1016/j.tcb.2019.11.005 – ident: B30 doi: 10.1016/j.jbc.2023.105492 – ident: B40 doi: 10.1126/sciadv.add8928 – ident: B24 doi: 10.1126/scitranslmed.aal2463 – ident: B19 doi: 10.1056/NEJMoa1802905 – ident: B29 doi: 10.1093/bib/bbab260 – ident: B59 doi: 10.1016/j.cell.2021.01.048 – ident: B8 doi: 10.1158/1078-0432.CCR-21-0361 – ident: B57 doi: 10.1007/978-1-0716-0868-5_20 – ident: B43 doi: 10.4161/cc.4.7.1830 – ident: B53 doi: 10.1038/nsmb.1568 – ident: B49 doi: 10.1158/2159-8290.CD-19-0270 – ident: B62 doi: 10.1038/s41556-021-00723-9 – ident: B21 doi: 10.1038/nm.4292 – ident: B44 doi: 10.1128/MCB.02025-07 – ident: B47 doi: 10.1158/2159-8290.CD-19-1228 – ident: B2 doi: 10.1200/JCO.2007.14.4147 – ident: B61 doi: 10.1016/j.cell.2023.11.022 – ident: B45 doi: 10.1016/j.cmet.2020.01.006 – ident: B4 doi: 10.1136/bmj-2022-071674 – ident: B15 doi: 10.1021/acs.jmedchem.1c00067 – ident: B6 doi: 10.1038/s41467-021-27559-z – ident: B13 doi: 10.1016/j.celrep.2016.03.043 – ident: B63 doi: 10.1016/j.cmet.2014.03.017 – ident: B1 doi: 10.1007/978-1-0716-0904-0_5 – ident: B16 doi: 10.1038/s41571-020-00452-2 – ident: B22 doi: 10.1016/j.cell.2018.11.024 – ident: B28 doi: 10.1016/j.annonc.2021.09.019 – ident: B37 doi: 10.1074/jbc.M702287200 – ident: B9 doi: 10.1016/j.ccell.2019.05.014 – ident: B32 doi: 10.1016/j.cell.2017.05.003 – ident: B7 doi: 10.1016/j.apsb.2022.03.026 – ident: B14 doi: 10.1021/acs.jmedchem.0c01895 – ident: B26 doi: 10.1172/JCI177357 – ident: B58 doi: 10.1038/nrm.2017.48 – ident: B11 doi: 10.1126/science.aad5944 |
| SSID | ssj0014454 |
| Score | 2.4952605 |
| Snippet | Triple-negative breast cancer (TNBC) represents the most malignant subtype of breast cancer. The clinical application of PARP inhibitors (PARPi) is limited by... |
| SourceID | doaj pubmedcentral proquest gale pubmed crossref |
| SourceType | Open Website Open Access Repository Aggregation Database Index Database Enrichment Source |
| StartPage | 1 |
| SubjectTerms | 5'-Methylthioadenosine phosphorylase Animals Antineoplastic drugs Biomarkers Brain Neoplasms - drug therapy Brain Neoplasms - genetics Brain Neoplasms - secondary BRCA1 protein Breast cancer Cancer Cancer therapies Cell Line, Tumor Chemotherapy Cyclin-dependent kinases DNA damage DNA methylation DNA repair DNA Repair - drug effects Drug dosages Female Gene deletion Genotoxicity Health aspects Humans Kinases Medical prognosis Metabolism Metastases Metastasis Methionine Methionine Adenosyltransferase - genetics Methionine Adenosyltransferase - metabolism Methyltransferases - genetics Methyltransferases - metabolism Mice Mice, Knockout MRE11 protein Mutation Neoplasm Proteins - antagonists & inhibitors Neoplasm Proteins - genetics Neoplasm Proteins - metabolism Oncology Oncology, Experimental Patients Poly(ADP-ribose) polymerase Poly(ADP-ribose) Polymerase Inhibitors - pharmacology S-Adenosylmethionine S-Adenosylmethionine - metabolism Therapeutics Toxicity Transferases Triple Negative Breast Neoplasms - drug therapy Triple Negative Breast Neoplasms - enzymology Triple Negative Breast Neoplasms - genetics Triple Negative Breast Neoplasms - metabolism Triple Negative Breast Neoplasms - pathology |
| SummonAdditionalLinks | – databaseName: Biological Science Database dbid: M7P link: http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwpV3fb9MwELZgIMTL-A2BAQYh2Eu0xHF--AmViYkhbVSjoL1ZjuN0laaki1Mk_nvuXDcsYkJIPFWtP1dJbN-dfV--I-RNXiZ1KpQJdc5NyHUES6osTQjRbw3ht-FJzV2xifz4uDg9FVN_4GY9rXJjE52hrlqNZ-R7Cbh-lHJh6fvlRYhVozC76ktoXCc3UCWBOeredMgicJ56FeY4FHlSeGUh8Nl7n_cP4wKcWzTyR062_0_jfMk7jZmTl1zRwZ3_vYm7ZNsHoXSynjX3yDXT3Ce3jnya_QGxM8cPB69Gj2aTKV00GFtaY-l0coJfzxYlWIKO2pV1tBjHsP0JDbTv8OQ-bMzcKYrTEjv2VOPk6qivCkQVrcFrhhAwI2mXnrft8iH5dvBxtv8p9NUZQp3lWR_yQscQ62mlTKSY5krAmEMQLJSuirTKsDR7LQoesxJiIMOYyEtmChEprSrolDwiW03bmCeEZigLl2BGVcOGDYIOoYVmsFHT8KeGs4DsbsZIai9djhU0zqXbwuRMDsMZkNcDdLnW67gK9AEHegCgxLb7oe3m0q9YqaLMqDovc_jEZKdSqo7LFKUuUq4rHpCXOE3k-n3VwVDISYEajBD44rU4BMpsNMjjmauVtfLwy_d_AH09GYHeeVDdwo1r5d-dgMeH8l0j5NsRcr4WL78KuDMCglXR4-bNDJbeqln5e_oG5NXQjD2RqdeYdoUYlDdCmm9AHq8Xy_CcuRMLikVAitEyGg3EuKVZnDnN85gxx6h8-vfrekZuMyzQ7PjUO2Sr71bmObmpf_QL271w1uEX575sBw priority: 102 providerName: ProQuest |
| Title | Targeting MTAP increases PARP inhibitor susceptibility in triple-negative breast cancer through a feed-forward loop |
| URI | https://www.ncbi.nlm.nih.gov/pubmed/40590219 https://www.proquest.com/docview/3232196925 https://www.proquest.com/docview/3226351074 https://pubmed.ncbi.nlm.nih.gov/PMC12208554 https://doaj.org/article/a06eaf7b706e4078aaaf1b5102354cd4 |
| Volume | 135 |
| WOSCitedRecordID | wos001530480600023&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: PRVAON databaseName: Directory of Open Access Journals customDbUrl: eissn: 1558-8238 dateEnd: 99991231 omitProxy: false ssIdentifier: ssj0014454 issn: 1558-8238 databaseCode: DOA dateStart: 20220101 isFulltext: true titleUrlDefault: https://www.doaj.org/ providerName: Directory of Open Access Journals – providerCode: PRVPQU databaseName: Biological Science Database (ProQuest) customDbUrl: eissn: 1558-8238 dateEnd: 99991231 omitProxy: false ssIdentifier: ssj0014454 issn: 1558-8238 databaseCode: M7P dateStart: 20020701 isFulltext: true titleUrlDefault: http://search.proquest.com/biologicalscijournals providerName: ProQuest – providerCode: PRVPQU databaseName: Health & Medical Collection (ProQuest) customDbUrl: eissn: 1558-8238 dateEnd: 99991231 omitProxy: false ssIdentifier: ssj0014454 issn: 1558-8238 databaseCode: 7X7 dateStart: 20020701 isFulltext: true titleUrlDefault: https://search.proquest.com/healthcomplete providerName: ProQuest – providerCode: PRVPQU databaseName: Nursing & Allied Health Database customDbUrl: eissn: 1558-8238 dateEnd: 99991231 omitProxy: false ssIdentifier: ssj0014454 issn: 1558-8238 databaseCode: 7RV dateStart: 20020701 isFulltext: true titleUrlDefault: https://search.proquest.com/nahs providerName: ProQuest – providerCode: PRVPQU databaseName: ProQuest Central Database Suite (ProQuest) customDbUrl: eissn: 1558-8238 dateEnd: 99991231 omitProxy: false ssIdentifier: ssj0014454 issn: 1558-8238 databaseCode: BENPR dateStart: 20020701 isFulltext: true titleUrlDefault: https://www.proquest.com/central providerName: ProQuest |
| link | http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwrV3fb9MwELZgIMQL4ucIjGIQAl6iJY4Tx4_dtIkhrUSlTH2LHNfpKk3JlLST9t9z57hRIybBAy-pWn-uUt_Zd66_fEfIJ1FEZSyV8bXgxuc6gClVFMaH7LeE9NvwqOS22ISYTNL5XGY7pb6QE9bJA3cDd6iCxKhSFAJe8cxJKVWGRYyKAzHXC6sEGgi53Uy58wPOY-50hCBCH34_PgtTCGXBIPpYkf4_l-KdWDTkSe4EntOn5InLGOm4u9Nn5J6pnpNH5-5M_AVpZ5bMDSGIns_GGV1VmAi2pqXZeIpvL1cFTNuGtpvWclgsHfYWGui6wb_Z_cosrfw3LbDjmmr0hIa6Ej5U0RJCnA_ZLTJs6VVdX78kv05PZsfffFdKwdeJSNY-T3UIiZlWygSKaa4kGAgyVqn0Io0XCdZRL2XKQ1ZAwmIYk6JgJpWB0moBnaJXZK-qK_Oa0AQ13CI8_tSwu4IMQWqpGeyqNHyp4cwjX7dDnGunM47lLq5yu98QLO-t4ZGPPfS6E9e4C3SEduoBqIdtPwAvyZ2X5H_zEo-8Ryvn3cOl_azOxykKJkKWivdiEaiJUSHpZqk2bZuf_bj4B9DP6QD0xYHKGn64Vu5BBxg-1NoaID8PkMtOafwu4MEACEuAHjZvnTd3S1CbR5Aro_YRiz3yoW_Gnkirq0y9QQxqESEn1yP7na_348ytsk8oPZIOZsHAEMOWanVpBcpDxiz98c3_MN1b8phhzWVLkT4ge-tmY96Rh_pmvWqbEbkvphd4nQt7TUfkwdHJJJuO7IIwQi5v9hu4HWHH |
| linkProvider | Directory of Open Access Journals |
| linkToHtml | http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMw1V1bb9MwFLbGQMAL90tgMIO4vURrHKdOHhAqg2lla5lGQX0zjut0laakJC1of4rfyDmOGxYxIV72wFPV-kvkJD63-st3CHkm0jCLEmV8Lbjxue6ASaWp8SH7zSD9NjzMuG02IYbDeDxODtbIz9W7MEirXPlE66gnhcb_yLdCCP0o5cKiN_NvPnaNwt3VVQuNelnsmZMfULJVr_vv4Pk-Z2zn_Wh713ddBXzdFd2Fz2MdQI6ilTIdxTRXCcwVkrdE6UkcTbrYUjxLYh6wFGK3YSwRKTNx0lFaTeCgEM57gVwEPy6w2BPjpsCD2iRyqs-Bn4gwdkpGkCNsfdjuBzEE004r_tk2AX8Gg1PRsM3UPBX6dq7_bzftBrnmkmzaq63iJlkz-S1yeeBoBLdJNbL8d4jadDDqHdBZjrlzZSp60DvEr0ezFDxdSatlZWk_lkF8AgN0UeLOhJ-bqVVMpykeuKAajaekrusRVTSDrMCHggBJyfS4KOZ3yOdzueS7ZD0vcnOf0C7K3oW4Y6yhIIWkKtGJZlCIajip4cwjr1ZrQmonzY4dQo6lLdEEk83y8cjTBjqv9UjOAr3FhdUAUELc_lCUU-k8klSdrlGZSAV84mauUioL0gilPCKuJ9wjm7gsZf0-buMIZS9GjUlI7HEuFoEyIjnylKZqWVWy__HLP4A-HbZALx0oK-DCtXLvhsDtQ3myFvJFCzmtxdnPAm60gOA1dXt4ZTHSee1K_jYXjzxphvFIZCLmplgiBuWbkMbskXu1cTb3mVsxpCDxSNwy29aDaI_ksyOr6R4wZhmjD_4-r01yZXc02Jf7_eHeQ3KVYTNqyx3fIOuLcmkekUv6-2JWlY-tZ6Lk63lb9S_MFcm8 |
| linkToPdf | http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMw1V1bb9MwFLZGhyZeuF8CgxnE7SVq4zhN_IBQd6koY6UqBe0tOK7TVZqSkrSg_TV-Hec4bljEhHjZA09V6y-R4_hcXH_-DiHPw8RPAyG1q0KuXa46YFJJol3IflNIvzX3U26KTYTDYXR8LEYb5Of6LAzSKtc-0Tjqaa7wP_K2D6EfpVxY0E4tLWK033-7-OZiBSncaV2X06imyKE--wHLt_LNYB_e9QvG-geTvXeurTDgqm7YXbo8Uh7kK0pK3ZFMcSmg35DICammUTDtYnnxVETcYwnEcc2YCBOmI9GRSk7hIh_ue4VshpBk8BbZ3D0Yjsb1HgbngdWA9lwR-pHVNYKMof1-b-BFEFo7jWhoigb8GRrOxcYmb_NcIOzf-J-H8Ca5btNv2qvs5RbZ0NltsnVkCQZ3SDkxzHiI5_Ro0hvReYZZdalLOuqN8evJPAEfWNByVRpCkOEWn0EDXRa4Z-Fmema01GmCFy6pQrMqqK2HRCVNIV9wYamAdGV6mueLu-TzpTzyPdLK8kw_ILSLgng-7iUrWKpCuiWUUAyWqApuqjlzyOv1_IiVFW3H2iGnsVm8hSyup5JDntXQRaVUchFoFydZDUBxcfNDXsxi66ti2elqmYZJCJ-4zSulTL0kQJGPgKspd8gOTtG4Oqlbu8i4F6H6JKT82BeDQIGRDOfZTK7KMh58_PIPoE_jBuiVBaU5PLiS9tQIDB8KlzWQLxvIWSXbfhFwuwEEf6qazWvria0_L-PfpuOQp3UzXokcxUznK8SgsBMSnB1yvzLUepy5kUnyhEOihgk3XkSzJZufGLV3jzHDJX34937tkC0w5vjDYHj4iFxjWKXakMq3SWtZrPRjclV9X87L4ol1U5R8vWyz_gXIntPc |
| 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=Targeting+MTAP+increases+PARP+inhibitor+susceptibility+in+triple-negative+breast+cancer+through+a+feed-forward+loop&rft.jtitle=The+Journal+of+clinical+investigation&rft.au=Zeng%2C+Xiangyu&rft.au=Zhao%2C+Fei&rft.au=Tu%2C+Xinyi&rft.au=Zhang%2C+Yong&rft.date=2025-07-01&rft.issn=1558-8238&rft.eissn=1558-8238&rft.volume=135&rft.issue=13&rft_id=info:doi/10.1172%2FJCI188120&rft.externalDBID=n%2Fa&rft.externalDocID=10_1172_JCI188120 |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1558-8238&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1558-8238&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1558-8238&client=summon |