Targeting Myc-driven stress vulnerability in mutant KRAS colorectal cancer (Ruan et al.)

Jian Yu & Hang Ruan
Mutant KRAS is a key driver in colorectal cancer (CRC) and promotes Myc translation and Myc-dependent stress adaptation and proliferation. Here, we report that the combination of two FDA-approved drugs Bortezomib and Everolimus (RAD001) (BR) is highly efficacious against mutant KRAS CRC cells. Mechanistically, the combination, not single agent, rapidly depletes Myc protein, not mRNA, and leads to GCN2- and p-eIF2a-dependent cell death through the activation of extrinsic and intrinsic apoptotic pathways. Cell death is...
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