| First Author | Murillo MM | Year | 2018 |
| Journal | Cell Rep | Volume | 25 |
| Issue | 13 | Pages | 3545-3553.e2 |
| PubMed ID | 30590030 | Mgi Jnum | J:270990 |
| Mgi Id | MGI:6278359 | Doi | 10.1016/j.celrep.2018.12.003 |
| Citation | Murillo MM, et al. (2018) Disruption of the Interaction of RAS with PI 3-Kinase Induces Regression of EGFR-Mutant-Driven Lung Cancer. Cell Rep 25(13):3545-3553.e2 |
| abstractText | RAS family GTPases contribute directly to the regulation of type I phosphoinositide 3-kinases (PI3Ks) via RAS-binding domains in the PI3K catalytic p110 subunits. Disruption of this domain of p110alpha impairs RAS-mutant-oncogene-driven tumor formation and maintenance. Here, we test the effect of blocking the interaction of RAS with p110alpha on epidermal growth factor receptor (EGFR)-mutant-driven lung tumorigenesis. Disrupting the RAS-PI3K interaction inhibits activation of both AKT and RAC1 in EGFR-mutant lung cancer cells, leading to reduced growth and survival, and inhibits EGFR-mutant-induced tumor onset and promotes major regression of established tumors in an autochthonous mouse model of EGFR-mutant-induced lung adenocarcinoma. The RAS-PI3K interaction is thus an important signaling node and potential therapeutic target in EGFR-mutant lung cancer, even though RAS oncogenes are not themselves mutated in this setting, suggesting different strategies for tackling tyrosine kinase inhibitor resistance in lung cancer. |
