2021 LCRF-AstraZeneca Research Grant
Justin Jee, MD, PhD
Memorial Sloan Kettering Cancer Center
Subclone Capture Sequencing to Guide Combination Therapy and Improve Osimertinib Response
Therapies such as osimertinib target specific tumor mutations found through DNA sequencing. This approach of matching patients to targeted therapies based on tumor DNA lowers mortality and morbidity and has transformed the treatment of lung cancer. However, tumors undergo constant mutation and evolution. Resistance to even the best targeted therapies is inevitable, often because a small minority of cells with mutations not covered by the initial targeted therapy emerges to drive tumor growth. These secondary mutant populations are nearly impossible to detect early in disease using standard approaches. This project will use newer, more sensitive DNA sequencing technology and sampling from multiple tumor areas to detect these minority populations in their infancy. Using such techniques, patients can be treated with combinations of therapies in the front-line setting based on their more detailed DNA profile, allowing for earlier, more stable disease control.