Combination PI3K/MEK inhibition promotes tumor apoptosis and regression in PIK3CA wild-type, KRAS mutant colorectal cancer.

Published

Journal Article

PI3K inhibition in combination with other agents has not been studied in the context of PIK3CA wild-type, KRAS mutant cancer. In a screen of phospho-kinases, PI3K inhibition of KRAS mutant colorectal cancer cells activated the MAPK pathway. Combination PI3K/MEK inhibition with NVP-BKM120 and PD-0325901 induced tumor regression in a mouse model of PIK3CA wild-type, KRAS mutant colorectal cancer, which was mediated by inhibition of mTORC1, inhibition of MCL-1, and activation of BIM. These findings implicate mitochondrial-dependent apoptotic mechanisms as determinants for the efficacy of PI3K/MEK inhibition in the treatment of PIK3CA wild-type, KRAS mutant cancer.

Full Text

Duke Authors

Cited Authors

  • Roper, J; Sinnamon, MJ; Coffee, EM; Belmont, P; Keung, L; Georgeon-Richard, L; Wang, WV; Faber, AC; Yun, J; Yilmaz, ÖH; Bronson, RT; Martin, ES; Tsichlis, PN; Hung, KE

Published Date

  • June 2014

Published In

Volume / Issue

  • 347 / 2

Start / End Page

  • 204 - 211

PubMed ID

  • 24576621

Pubmed Central ID

  • 24576621

Electronic International Standard Serial Number (EISSN)

  • 1872-7980

International Standard Serial Number (ISSN)

  • 0304-3835

Digital Object Identifier (DOI)

  • 10.1016/j.canlet.2014.02.018

Language

  • eng