Washington University in St. Louis (WU)
KRAS mutations are found in over 90% of pancreatic ductal adenocarcinoma (PDAC) cases, with KRAS^G12D being the most prevalent, making it a key therapeutic target. While recent KRAS inhibitors—targeting KRAS^G12C, KRAS^G12D, and RAS(ON)—have shown early promise, their clinical efficacy is limited by rapid development of resistance and modest response rates when used alone. To overcome these challenges, our research focuses on developing combination therapies that enhance the effectiveness of KRAS-MAPK inhibition and prevent both adaptive and acquired resistance. We aim to identify safe and potent drug combinations that can be used across different stages of PDAC progression. Additionally, my research program is expanding to explore how interactions between tumor cells and the microenvironment contribute to resistance. Using advanced tools like spatial transcriptomics, single-cell RNA sequencing, and integrative bioinformatics, we seek to uncover context-specific vulnerabilities that can be targeted therapeutically, ultimately improving outcomes for patients with KRAS-mutant PDAC.