ReachMD

I am the Director of the Center for Thoracic Cancers at MGH, Co-Leader of the Dana-Farber/MGH/Harvard Cancer Center Thoracic Oncology Program, and Co-Leader of the SU2C Lung Cancer Dream Team. As a basic science-trained physician and translational researcher, I have built a career at the precise intersection of clinical oncology and molecular genetics. My major research interests center on oncogene-driven lung cancers, particularly those harboring chromosomal rearrangements of anaplastic lymphoma kinase (ALK) or ROS1. In early studies, I showed that ALK and ROS1 define unique molecular subsets of lung cancer with marked sensitivity to the ALK/ROS1 inhibitor crizotinib. I was the lead clinical investigator for the registration studies of crizotinib which led to FDA approval of the drug for advanced ALK- and ROS1-rearranged NSCLC. In collaboration with basic laboratory investigators at MGH and the Broad Institute, my research has focused on elucidating mechanisms of resistance to crizotinib and other ALK targeted therapies. We have studied resistance using a number of model systems, including cell line models derived directly from resistant patient specimens. Our studies have revealed numerous new mechanisms of resistance and have guided the clinical development of second- and third-generation ALK inhibitors. I have served as the lead investigator on registration trials of three next generation agents for ALK-rearranged NSCLC (ceritinib, alectinib, and lorlatinib). Recent work has focused on tracking the evolution of resistance through sequential ALK targeted therapies and defining the extent of tumor heterogeneity within individual tumors and patients. In addition, current studies are now examining potential therapeutic combination strategies, several of which have entered the clinic for treatment-naïve and resistant patients.