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ARTICLE | Distillery Therapeutics

Inhibiting SHANK3 to induce signaling overdose in KRAS-mutant cancer

BC Staff
November 6, 2024 6:44 PM UTC

Targeting cancer cell SHANK3, a scaffold protein that competitively binds to normal and mutant active RAS to limit downstream MAPK/ERK signaling for optimal cell growth, could help treat KRAS-mutant cancers by hyper-activating ERK, which kills tumor cells via signaling overdose.

In a panel of human pancreatic, lung, and colorectal cancer cell lines, SHANK3 knockdown decreased cell proliferation compared with normal expression in cancer cells with KRAS mutations, but not in those with normal KRAS. ...

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