Epigenetic and Oncogenic Inhibitors Cooperatively Drive Differentiation and Kill KRAS-Mutant Colorectal Cancers

表观遗传和致癌抑制剂协同驱动分化并杀死 KRAS 突变型结直肠癌

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作者:Patrick Loi #, Amy E Schade #, Carrie L Rodriguez, Anjana Krishnan, Naiara Perurena, Van T M Nguyen, Yilin Xu, Marina Watanabe, Rachel A Davis, Alycia Gardner, Natalie F Pilla, Kaia Mattioli, Olesja Popow, Nuray Gunduz, Tamsin R M Lannagan, Samantha Fitzgerald, Ewa T Sicinska, Jia-Ren Lin, William T

Abstract

Combined EZH2 and RAS pathway inhibitors kill KRAS-mutant colorectal cancer cells and promote durable tumor regression in vivo. These agents function by cooperatively suppressing the WNT pathway, driving differentiation, and epigenetically reprogramming cells to permit the induction of apoptotic signals, which then kill these more differentiated tumor cells.

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