Stanford Cancer Institute

SCI Pancreatic Cancer Innovation Award

March 2024

Gerald Crabtree, MD, David Korn, MD, Professor of Pathology and professor of developmental biology, and Nathanael Gray, PhD, Krishnan-Shah Family Professor of chemical and systems biology, were awarded an SCI Pancreatic Cancer Innovation Award for their project, “Rewiring RAS pathway mutations to activate programmed cell death in pancreatic cancer.” Crabtree studies chromatin regulation in development and human cancer. Gray utilizes the tools of synthetic chemistry, protein biochemistry, and cancer biology to discover and validate new cancer drugs. 

Genes in the RAS pathway regulate the growth, differentiation, and survival of cells. The overactivation of the RAS pathway therefore can lead to cancer. Indeed, approximately 95% of pancreatic cancers are driven by mutations in genes within the RAS pathway. However, because the RAS pathway also functions in normal cells, it has been challenging to develop drugs that specifically impact RAS activity in tumors without also harming normal cells. Crabtree and Gray, with the support of the SCI Pancreatic Cancer Innovation Award, are taking a creative approach to address this challenge. They plan to use the specific overactivation of RAS in cancer cells to target these same cells.  They will use specifically developed small molecules to re-wire the RAS pathway, such that, instead of promoting growth, it activates a cellular program causing cell death.  Importantly, these molecules will only kill cells containing the overactive RAS pathway. Because mutations causing RAS pathway overactivity are unique to cancer cells, these small molecules should kill cancer cells without harming normal cells.