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

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.