Roger Lo, MD, PhD
Professor, Department of Dermatology, UCLA
Linking Cellular and Genomic Mechanisms of Acquired Resistance to KRAS Inhibition in PDAC
Project Summary:
Roger Lo, MD, PhD, is a Professor of Medicine (Dermatology) and Molecular & Medical Pharmacology at UCLA. Renowned for his research on drug resistance in melanoma, Dr. Lo brings his expertise in cancer signaling and therapy resistance to pancreatic cancer research.
Mutations in the KRAS gene drive more than 90% of pancreatic cancers and for decades was considered “undruggable.” Recent breakthroughs have finally led to promising KRAS inhibitors, but unfortunately, most patients develop resistance soon after treatment begins.
Dr. Roger Lo’s research, supported by the Catalyst Grant Program, aims to understand and overcome this drug resistance. Drawing on his previous work in melanoma, Dr. Lo discovered that targeted therapies can cause genomic instability, enabling cancer cells to acquire more genetic mutations and escape treatment.
His current project investigates whether KRAS inhibitors in pancreatic cancer trigger similar genomic instability. He will also explore whether combining KRAS inhibitor drugs with drugs that stabilize cancer cell genomes, such as ROCK inhibitors, can limit acquired resistance and extend treatment responses.
Using both pancreatic cancer cell lines and patient-derived models, Dr. Lo’s team will identify the molecular mechanisms behind resistance and discover potential biomarkers to guide future combination therapies. The findings could help extend survival for patients receiving KRAS-targeted treatments.
