We are investigating the broader Ras pathway in the context of Non-Small Cell Lung Cancer (NSCLC). Ras mutations are found in roughly a third of human cancers, but are notoriously “undruggable”. Efforts to treat Ras-mutant cancers with drugs targeting downstream effectors have hitherto been unsuccessful*. While PI(3) Kinase and Raf have received the lion’s share of investigation, other proteins are known to bind to Ras but have received little attention.
Leveraging our AP/MS (LINK) and Bioinformatics (LINK) capabilities, we seek to map out interactions surrounding Ras pathway genes to better understand their functions. The Jackson Lab is also a member of the National Cancer Institute Ras Initiave, and Cancer Cell Map Initiative. In collaboration with the laboratory of Dr. Michael Bassik, we are developing CRISPR Dual Knockout (CDKO) libraries to systematically identify genetic interactions between genes identified in our AP/MS data. Together, these data point to new cell biological roles for Ras, clarify the mechanism of known Ras-driven phenotypes, and point to vulnerabilities that future therapies may exploit.
*For a discussion of these issues, see this article