Research ArticleCancer

Application of a MYC degradation screen identifies sensitivity to CDK9 inhibitors in KRAS-mutant pancreatic cancer

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Science Signaling  16 Jul 2019:
Vol. 12, Issue 590, eaav7259
DOI: 10.1126/scisignal.aav7259

Screening tumor vulnerability

Mutations in the gene encoding the guanosine triphosphatase KRAS are common drivers of various cancers. Because most mutant KRAS proteins are currently too difficult to therapeutically target, alternative targets in KRAS-mutant tumors must be identified. Given a previous observation that KRAS-mutant pancreatic cancers (PDACs) rely on the transcription factor MYC, Blake et al. screened for inhibitors that decreased MYC protein abundance. They found that an inhibitor of the cell cycle–associated kinase CDK9 decreased MYC abundance at both the mRNA and protein levels in a manner independent of KRAS signaling itself. This finding reveals a potential therapeutic target for patients with KRAS-mutant PDAC and possibly also those with more generally MYC-dependent cancers.

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