2021 LCRF-AstraZeneca Research Grant
Justin Jee, MD, PhD
Memorial Sloan Kettering Cancer Center
Research Project:
Subclone Capture Sequencing to Guide Combination Therapy and Improve Osimertinib Response
Summary:
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.
Update:
The goal of the project was to try and identify resistant clones of cells in pre-treatment samples to direct different treatment combinations with osimertinib for initial treatment. 46 human tissue samples have been examined. In 2 samples low levels of treatment resistant drivers were found. Research is still underway. There was one presentation at the ASCO meeting in 2023 and the researcher has been awarded an ASCO Young Investigator award based on the preliminary work.
Impact:
This research could have an impact on the initial treatment of EGFRmut+ NSCLC. By identifying potentially resistant clones of cells pre-treatment, various drug combinations could be delivered to address resistant cancer cells early in the initial treatment. If the researcher is successful in identifying the resistant cells, these findings could result in a clinical trial that would address this approach to treatment.