The impact of genomic changes on the targeted treatment of thoracic malignancies
My research is based on my multiple responsibilities as the leader of the Lung Cancer Program at the Harvard Medical School affiliated institutions. In my past role as Director of the Lowe Center for Thoracic Oncology at the Dana-Farber Cancer Institute, I have been responsible for fostering collaborative research across the clinical disciplines, integrating population and basic science into our research programs, and applying innovative therapeutic strategies into the treatment of our patients with lung cancer. I have led the Lung Cancer Program within the Dana-Farber/Harvard Cancer Center from a Program in Development to a full Program and was part of the successful Dana-Farber/ Harvard Cancer Center Grant competitive renewal in 2011 and received an exceptional rating. Under my leadership, the Lung Cancer Program has been able to increase its NIH funding 5 fold in the last 16 years. In addition, the Dana-Farber/Harvard Cancer Center Lung Cancer Program successfully renewed the Lung Cancer Specialized Program of Research Excellence Grant (SPORE) in 2008 and will submit the application in the fall 2016. My translational research is devoted to testing novel therapeutic agents for their efficacy against lung cancer and other thoracic malignancies with specific genomic changes. I provide care in our Center for patients with thoracic malignancies one day per week. I also lecture widely on my research and treatment of patients with lung cancer.
Members of our research group identified the link between mutations of the epidermal growth factor receptor and response to the epidermal growth factor receptor tyrosine kinase inhibitors, gefitinib and erlotinib. Subsequent research has now changed the paradigm of treatment for patients with non-small cell lung cancer and sensitizing mutations of the epidermal growth factor receptor so the standard of care around the world is to get treated with erlotinib or gefitinib rather than chemotherapy. I am one of the patent holders of the test and now more than 50% of all the patients with nonsquamous non-small cell lung cancer get the test.
The systematic characterization of the genomic changes in lung cancer has now identified multiple changes that can lead to treatment with approved targeted agents (gefitinib and erlotinib) or enrollment onto ongoing investigation studies. These include EGFR, KRAS, HER2, BRAF, and PIK3CA mutations as well as the ALK and ROS1 rearrangements. I worked with members of our research group to set up systematic genomic characterization of nearly all of our advanced non-small cell lung cancer patients for EGFR, KRAS, HER2, BRAF, PI3KA mutations, ALK and ROS1 rearrangements, plus HER2 and MET amplification. We now characterize these genomic changes in 30-50 patients per month, track the results, are working toward placing them in the medical record, and preferentially steering these patients into appropriate genomically based protocols. It is our goal to treat a quarter of our patients with non-small cell lung cancer with targeted agents.