| First Author | Corcoran RB | Year | 2013 |
| Journal | Cancer Cell | Volume | 23 |
| Issue | 1 | Pages | 121-8 |
| PubMed ID | 23245996 | Mgi Jnum | J:194363 |
| Mgi Id | MGI:5473479 | Doi | 10.1016/j.ccr.2012.11.007 |
| Citation | Corcoran RB, et al. (2013) Synthetic lethal interaction of combined BCL-XL and MEK inhibition promotes tumor regressions in KRAS mutant cancer models. Cancer Cell 23(1):121-8 |
| abstractText | KRAS is the most commonly mutated oncogene, yet no effective targeted therapies exist for KRAS mutant cancers. We developed a pooled shRNA-drug screen strategy to identify genes that, when inhibited, cooperate with MEK inhibitors to effectively treat KRAS mutant cancer cells. The anti-apoptotic BH3 family gene BCL-XL emerged as a top hit through this approach. ABT-263 (navitoclax), a chemical inhibitor that blocks the ability of BCL-XL to bind and inhibit pro-apoptotic proteins, in combination with a MEK inhibitor led to dramatic apoptosis in many KRAS mutant cell lines from different tissue types. This combination caused marked in vivo tumor regressions in KRAS mutant xenografts and in a genetically engineered KRAS-driven lung cancer mouse model, supporting combined BCL-XL/MEK inhibition as a potential therapeutic approach for KRAS mutant cancers. |
