Article
Failure to induce apoptosis via BCL-2 family proteins underlies lack of efficacy of combined MEK and PI3K inhibitors for KRAS-mutant lung cancers.
Cancer research - 1 Jun 2014
Hata Aaron N, Yeo Alan, Faber Anthony C, Lifshits Eugene, Chen Zhao, Cheng Katherine A, Walton Zandra, Sarosiek Kristopher A, Letai Anthony, Heist Rebecca S, Mino-Kenudson Mari, Wong Kwok-Kin, Engelman Jeffrey A
Abstract excerpt
Although several groups have demonstrated that concomitant use of MEK and phosphoinositide 3-kinase (PI3K) inhibitors (MEKi/PI3Ki) can induce dramatic tumor regressions in mouse models of KRAS-mutant non-small cell lung cancer (NSCLC), ongoing clinical trials investigating this strategy have been underwhelming to date. While efficacy may be hampered by a narrow therapeutic index, the contribution of biologic...
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