4.7 Review

Capitalizing on Synthetic Lethality of MYC to Treat Cancer in the Digital Age

Journal

TRENDS IN PHARMACOLOGICAL SCIENCES
Volume 42, Issue 3, Pages 166-182

Publisher

CELL PRESS
DOI: 10.1016/j.tips.2020.11.014

Keywords

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Funding

  1. National Research Foundation Cancer Science Institute of Singapore RCE Main Grant, Ministry of Education Academic Research Fund (MOE AcRF Tier 2) [MOE2019-T2-1-115]
  2. NRF Competitive Research Programme [NRF-CRP-2017-05]
  3. Singapore Ministry of Health's National Medical Research Council [MOH-OFLCG18May-0003, MOH-OFLCG18May-0028]

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Deregulation of MYC is a common oncogenic driver in cancer, and developing targeted therapies against MYC is a critical unmet need in cancer treatment. Synthetic lethality shows promise in targeting MYC-dependent vulnerabilities, but translating it to the clinic remains challenging.
Deregulation of MYC is among the most frequent oncogenic drivers of cancer. Developing targeted therapies against MYC is, therefore, one of the most critical unmet needs of cancer therapy. Unfortunately, MYC has been labelled as undruggable due to the lack of success in developing clinically relevant MYC-targeted therapies. Synthetic lethality is a promising approach that targets MYC-dependent vulnerabilities in cancer. However, translating the synthetic lethality targets to the clinics is still challenging due to the complex nature of cancers. This review highlights the most promising mechanisms of MYC synthetic lethality and how these discoveries are currently translated into the clinic. Finally, we discuss how in silico computational platforms can improve clinical success of synthetic lethality-based therapy.

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