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Systematic Analysis of Drug Vulnerabilities Conferred by Tumor Suppressor Loss

Hongyu Ding1, Jie Zhao1, Yanli Zhang1

  • 1State 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.

Cell Reports
|June 13, 2019
PubMed

Insights

Targeting tumor suppressor loss offers new cancer precision medicine avenues. A systematic drug sensitivity map reveals how losing tumor suppressors affects cancer drug responses, guiding new therapeutic strategies.

Area of Science:

  • Oncology
  • Genetics
  • Pharmacology

Background:

  • Targeting oncogenes is a cornerstone of precision cancer medicine.
  • Understanding tumor suppressor deficiency's role in drug response is crucial.
  • The full spectrum of drug vulnerabilities from tumor suppressor loss is not well-defined.

Purpose of the Study:

  • To systematically analyze the impact of tumor suppressor loss on cellular sensitivity to various anticancer drugs.
  • To generate a comprehensive drug sensitivity map based on tumor suppressor status.
  • To identify novel drug vulnerabilities associated with specific tumor suppressor deficiencies.

Main Methods:

  • Systematic analysis of 59 common tumor suppressors.
  • Testing cellular sensitivity to 26 different anticancer therapeutics in a one-gene, one-drug approach.
  • Delineation of mechanisms underlying gene-drug interactions.

Main Results:

  • Generated a drug sensitivity map detailing numerous instances of drug resistance and hypersensitivity.
  • Identified specific tumor suppressor losses that confer altered sensitivity to anticancer agents.
  • Elucidated mechanisms by which tumor suppressor loss modulates drug sensitivity at different stages of drug action.

Conclusions:

  • Tumor suppressor loss significantly impacts cancer drug sensitivity, creating both resistance and hypersensitivity.
  • The generated drug sensitivity map provides a valuable resource for expanding precision cancer medicine.
  • Leveraging tumor suppressor status can guide the selection of effective anticancer therapeutics.
Keywords:
BAP1CREBBPSETD2drug sensitivitytumor suppressor

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