Article
mTOR inhibition specifically sensitizes colorectal cancers with KRAS or BRAF mutations to BCL-2/BCL-XL inhibition by suppressing MCL-1.
Cancer discovery - 1 Jan 2014
Faber Anthony C, Coffee Erin M, Costa Carlotta, Dastur Anahita, Ebi Hiromichi, Hata Aaron N, Yeo Alan T, Edelman Elena J, Song Youngchul, Tam Ah Ting, Boisvert Jessica L, Milano Randy J, Roper Jatin, Kodack David P, Jain Rakesh K, Corcoran Ryan B, Rivera Miguel N, Ramaswamy Sridhar, Hung Kenneth E, Benes Cyril H, Engelman Jeffrey A
Abstract excerpt
Colorectal cancers harboring KRAS or BRAF mutations are refractory to current targeted therapies. Using data from a high-throughput drug screen, we have developed a novel therapeutic strategy that targets the apoptotic machinery using the BCL-2 family inhibitor ABT-263 (navitoclax) in combination with a TORC1/2 inhibitor, AZD8055. This combination leads to efficient apoptosis specifically in KRAS- and BRAF-mutant...
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