Identifying non-genomic mechanisms of RET TKI resistance

Grant title (if any)
Hamoui Foundation / LUNGevity Lung Cancer Research Award
Alexander Drilon, MD
Memorial Sloan Kettering Cancer Center
New York

Many RET-positive cancers become resistant to targeted therapy for reasons not clearly based on genetic changes alone. Dr. Drilon predicts that other causes of resistance include (1) chemical changes (in the “epigenome”) that turn cancer-causing genes on or off and (2) changes in how these cancers look under the microscope (“histology”) that affect cancer behavior. Because these changes affect cell states rather than mutations, this resistance is potentially reversible, defining a key opportunity to maintain, restore, and extend sensitivity to potent and specific RET inhibitors.