Chris O’Gorman’s Choosing to Make a Difference
Read moreState: Massachusetts
Sandra S. Zinkel, M.D., Ph.D.
Ricardo C.T. Aguiar, M.D., Ph.D.
Steven Zeitels, M.D., FACS
Funded by the Dick Vitale Gala
Thomas Look, M.D.
Funded by The V Foundation Wine Celebration
In honor of Teri Kuhn
Lynda Chin, M.D.
Akiko Shimamura, M.D., Ph.D.
Steven Barthel, Ph.D.
The precision oncology approach to the treatment of cancer bases treatment decisions on the biology of an individual’s cancer, most often using genetic alterations or mutations to inform therapy. This approach has been successful in a few cancer types, including lung cancer, melanoma, and chronic myelogenous leukemia where oral targeted therapies have led to both improved patient outcomes and fewer side effects compared to standard chemotherapy. However, this approach has not yet realized its full potential in these or other cancer types. In this proposal we plan to study new cancer-causing gene mutations involving the NTRK1, NTRK2 and NTRK3 genes, which are found in numerous types of cancer. We have already demonstrated that tumor cells treated with targeted therapies against this gene family can kill cancer cells in the laboratory. We have also observed early and dramatic tumor shrinkage in patients with different tumor types that share mutations in these NTRK genes. This proposal will focus on determining additional mutations of NTRK genes that may respond to therapy. The proposal will also study how cancer cells become resistant to targeted therapies and develop new laboratory models of NTRK+ cancer to develop new therapies for these cancers.
Ravindra Uppaluri, M.D., Ph.D.
One of the most exciting frontiers in cancer treatment is the field of immunotherapy where beneficial effects have been observed in a broad range of cancers. The major goal of our project is to identify the determinants of immunotherapy success in patients with head and neck cancers. We are performing a novel clinical trial with an immunotherapy-targeted agent that allows the patient’s own immune system to control their cancer. Using samples from this trial, our goal is to understand why some patients do or do not respond to immunotherapy. We have assembled a multi-disciplinary team that will use genetic and immunologic tests on patient samples to clarify which patients may actually benefit from this powerful approach. These data will allow us to define a precision approach to immunotherapy and in addition will provide an improved biologic understanding of the mechanism of immunotherapeutic modalities.
Matthew Meyerson, M.D., Ph.D.
Funded by the Stuart Scott Memorial
Cancer Research Fund
Lung cancer is the top cancer killer in the United States and worldwide, claiming over 1.5 million lives in 2012, according to the World Health Organization. The purpose of our research project is to understand how patients’ genetic ancestry contributes to the likelihood of acquiring specific harmful changes in DNA (“mutations”) in lung cells that lead to lung cancer. Mutations in the EGFR gene are important because EGFR mutations often cause lung cancer, especially in non-smokers. Significantly, patients whose lung cancers have EGFR mutations benefit from drugs targeting mutant EGFR, including gefitinib, erlotinib, and afatinib. Mutations in EGFR occur more frequently in lung cancer patients of East Asian or Latin American origin but the basis for this observation is a mystery, especially because these mutations are not inherited but arise after birth. Here, we propose to analyze DNA from 1500 Latin American lung cancer patients, to understand whether and how their genetic makeup leads to increased risk of developing EGFR-mutant lung cancer.
By defining the basis of increased risk of EGFR mutant lung cancer in Latin American populations, we could enable the use of effective existing treatments in this population. Additionally, if we can find a genetic marker for susceptibility to EGFR mutation, we could facilitate the screening, early detection and early EGFR-targeted therapy of lung cancer in at-risk populations. We therefore believe that our research plan could lead not only to an improved intellectual understanding of lung cancer but to improved outcomes for lung cancer patients from susceptible populations.
