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...

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Bibliographic Details
Published in:	The Journal of clinical investigation Vol. 135; no. 13; pp. 1 - 18
Main Authors:	Zeng, Xiangyu, Zhao, Fei, Tu, Xinyi, Zhang, Yong, Yang, Wen, Hou, Jing, Jiang, Qi, Zhu, Shouhai, Wu, Zheming, Hao, Yalan, Zhang, Lingxin, Weinshilboum, Richard M., Tao, Kaixiong, Wang, Liewei, Lou, Zhenkun
Format:	Journal Article
Language:	English
Published:	United States American Society for Clinical Investigation 01.07.2025
Subjects:	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 China Oncology Breast cancer Amino acid metabolism DNA repair Therapeutics
ISSN:	1558-8238, 0021-9738, 1558-8238
Online Access:	Get full text
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