Henning Willers, M.D.
Massachusetts General Hospital
Funded in partnership with the American Lung Association of the Northeast and the American Thoracic Society
Attacking Lung Cancer Before It Develops Drug Resistance
Targeted drugs like erlotinib commonly shrink lung cancers that depend on mutated EGFR (EGFRmut). However, invariably cancer cells survive, become drug resistant and cause tumor regrowth. In this study, we propose attacking the tumor before drug resistance and recurrence occur. We will take advantage of a unique clinical trial that allows us to biopsy EGFRmut tumors before drug resistance develops. Coupled with laboratory studies we will find out how tumor cells manage to survive the targeted therapy and how we can disrupt this ability. Our research may lead to a dramatic change in how we treat EGFRmut cancers, thereby prolonging lives and perhaps even achieving cures in some patients.
Update: Tyrosine kinase inhibitors (TKI) commonly shrink lung cancers that depend on mutated EGFR. However, tumor cells that initially survive drug treatment can persist and adapt to develop genetic mechanisms of resistance. Our initial findings support the idea that tumors with different TKI resistance mechanisms share a common dependency on PARP1, a protein with multiple roles aimed at helping cells to survive various forms of damage and stress. Our data suggest that the administration of PARP1 inhibitors may be a promising treatment approach for patients with EGFR-mutant lung cancers. Confirmatory studies in the laboratory and on tumor biopsies from a clinical trial are ongoing. Ultimately, our findings could lead to a dramatic change in how we treat these tumors, thereby prolonging lives and ultimately perhaps even achieving cures in some patients.