| First Author | Kruspig B | Year | 2018 |
| Journal | Sci Transl Med | Volume | 10 |
| Issue | 446 | PubMed ID | 29925636 |
| Mgi Jnum | J:263858 | Mgi Id | MGI:6188818 |
| Doi | 10.1126/scitranslmed.aao2565 | Citation | Kruspig B, et al. (2018) The ERBB network facilitates KRAS-driven lung tumorigenesis. Sci Transl Med 10(446) |
| abstractText | KRAS is the most frequently mutated driver oncogene in human adenocarcinoma of the lung. There are presently no clinically proven strategies for treatment of KRAS-driven lung cancer. Activating mutations in KRAS are thought to confer independence from upstream signaling; however, recent data suggest that this independence may not be absolute. We show that initiation and progression of KRAS-driven lung tumors require input from ERBB family receptor tyrosine kinases (RTKs): Multiple ERBB RTKs are expressed and active from the earliest stages of KRAS-driven lung tumor development, and treatment with a multi-ERBB inhibitor suppresses formation of KRAS(G12D)-driven lung tumors. We present evidence that ERBB activity amplifies signaling through the core RAS pathway, supporting proliferation of KRAS-mutant tumor cells in culture and progression to invasive disease in vivo. Brief pharmacological inhibition of the ERBB network enhances the therapeutic benefit of MEK (mitogen-activated protein kinase kinase) inhibition in an autochthonous tumor setting. Our data suggest that lung cancer patients with KRAS-driven disease may benefit from inclusion of multi-ERBB inhibitors in rationally designed treatment strategies. |
