Daniel L. Abravanel, MD, PhD
Dana-Farber Cancer Institute – Harvard Medical School
Metastatic breast cancer (MBC) – breast cancer that has spread to other organs – unfortunately remains incurable. In spite of the increasing number of treatments available that can benefit patients with MBC, the disease eventually develops resistance to each therapy. As such, there is a critical need to characterize resistance in patients as insights have the potential for rapid translation to improve quality of life and survival.
Most breast cancers express the estrogen receptor (ER). As these depend on estrogen, hormonal therapies are a mainstay of treatment. However, their efficacy is also limited by resistance. In fact, most breast cancer-related deaths result from ER+ MBC that develops resistance to hormonal therapy. One apparent pathway to resistance in ER+ tumors is for the cancer to become ER-negative. This phenomenon of “ER loss” impacts a substantial number of patients, limits treatment options, and is associated with worse outcomes, but remains poorly understood.
In this project we aim to characterize two fundamental aspects of ER loss by combining direct evaluation of biopsy samples from patients whose tumors exhibit ER loss with mechanistic studies in breast cancer cell lines: 1) the causes of ER loss, and 2) the ways that tumors continue to progress following ER loss. The long-term goal of this work is to direct the development of more effective treatments. Identifying the mechanisms by which tumors grow following ER loss should reveal new ways to treat tumors that have lost ER and understanding the causes of ER loss could enable the development of therapeutic strategies to delay or even prevent ER loss.
Dr. Abravanel received his undergraduate degree from Duke University in 2006, followed by a PhD in Cell and Molecular Biology and an MD through the University of Pennsylvania Medical Scientist Training Program. He went on to complete a residency in Internal Medicine at Brigham and Women’s Hospital. He is currently a fellow in Medical Oncology in the Dana-Farber/Mass General Brigham program. In 2018 he joined the laboratories of Dr. Nikhil Wagle and Dr. Joan Brugge as a postdoctoral fellow, where his research focuses on the role of intratumor heterogeneity in metastatic breast cancer progression and therapeutic resistance.