The 2017 Robert F. Gagel Discovery Award has been granted to Dr. Sareh Parangi, MD,
Dr. Parangi is a highly accomplished endocrine surgeon at Massachusetts General Hospital and Harvard Medical School in Boston. She focuses her clinical efforts on endocrine surgery and applies her basic science knowledge and expertise to tumor progression in thyroid cancer. Her proposal is titled, “Investigation of the role of myeloid-derived suppressor cells in the response to targeted therapies in advanced thyroid cancer.”
While targeted therapies for advanced cases of thyroid cancer have shown considerable progress, some cancers remain difficult to treat and drug resistance commonly emerges. Increased attention is focused on how tumor evasion of the immune system contributes to thyroid cancer growth, metastasis, and drug resistance. Immunotherapies have been developed to facilitate detection of tumors by immune cells, leading to improved tumor recognition and improved patient survival in various cancer types. These strategies typically employ a combination therapy designed to target both the tumor and the immune response. Unfortunately, resistance to immunotherapy has also been observed, and identifying indicators of response and mechanisms of resistance is urgently needed to design rational combination therapies that might circumvent resistance.
The overall goal of Dr. Parangi’s work is to harness the power of the immune system to help treat cancer. In particular she is focused on myeloid-derived suppressor cells (MDSCs), which are a population of circulating immature myeloid cells that have been detected in the peripheral blood of differentiated and anaplastic thyroid cancer patients. MDSCs appear to correlate with disease stage, and have been implicated in tumor development and resistance to targeted therapy. In her proposed work she will first characterize the functional significance of MDSCs in the tumor environment to help elucidate what these cell types are doing in a cancer setting. She will also assess whether depletion of MDSCs will augment the effectiveness of targeted therapies, adding another layer of treatment strategy for drug resistant cancers. The proposed study also aims to ascertain whether MDSCs can be used as a marker of antitumor immune response in patients undergoing targeted therapy. To this end, she will utilize novel ex vivo models, developed in collaboration with the Barbie lab at Dana Farber Cancer Institute, in which cells harvested from tumors of patients undergoing therapy are cultured and evaluated, enabling researchers to assess specifically how patients immune cells are responding to a specific therapy.