2. Academic Validation
  3. Systematic Analysis of Drug Vulnerabilities Conferred by Tumor Suppressor Loss

Systematic Analysis of Drug Vulnerabilities Conferred by Tumor Suppressor Loss

  • Cell Rep. 2019 Jun 11;27(11):3331-3344.e6. doi: 10.1016/j.celrep.2019.05.043.
Hongyu Ding 1,  Jie Zhao 1,  Yanli Zhang 1,  Jiao Yu 1,  Mingxian Liu 1,  Xiaoxi Li 1,  Liang Xu 1,  Minghui Lin 1,  Chuan Liu 1,  Zhengjin He 1,  Shishuang Chen 1,  Hai Jiang 2
Affiliations

Affiliations

  • 1 State Key Laboratory of Cell Biology, Key Laboratory of Systems Biology, Innovation Center for Cell Signaling Network, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China.
  • 2 State Key Laboratory of Cell Biology, Key Laboratory of Systems Biology, Innovation Center for Cell Signaling Network, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China. Electronic address: hai@sibcb.ac.cn.
PMID: 31189115 DOI: 10.1016/j.celrep.2019.05.043
Abstract

In addition to oncogene inhibition, targeting tumor suppressor deficiency could provide potential venues for precision Cancer medicine. However, the full spectrum of drug vulnerability conferred by tumor suppressor loss remains unclear. We systematically analyzed how loss of 59 common tumor suppressors each affected cellular sensitivity to 26 different types of Anticancer therapeutics. The experiments were performed in a one-gene, one-drug manner, and through such a large gene-drug iteration study, we were able to generate a drug sensitivity map that describes numerous examples of drug resistance or hypersensitivity conferred by tumor suppressor loss. We further delineated the mechanisms of several gene-drug interactions, showing that loss of tumor suppressors could modify drug sensitivity at various steps of drug action. This systematic drug sensitivity map highlights potential drug vulnerabilities associated with tumor suppressor loss, which may help expand precision Cancer medicine on the basis of tumor suppressor status.

Keywords

BAP1; CREBBP; SETD2; drug sensitivity; tumor suppressor.

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