| First Author | Roper J | Year | 2014 |
| Journal | Cancer Lett | Volume | 347 |
| Issue | 2 | Pages | 204-11 |
| PubMed ID | 24576621 | Mgi Jnum | J:210526 |
| Mgi Id | MGI:5571408 | Doi | 10.1016/j.canlet.2014.02.018 |
| Citation | Roper J, et al. (2014) Combination PI3K/MEK inhibition promotes tumor apoptosis and regression in PIK3CA wild-type, KRAS mutant colorectal cancer. Cancer Lett 347(2):204-11 |
| abstractText | 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. |
