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Daniel L. Abravanel, MD, PhD

Medical Oncology Fellow
Dana‐Farber Cancer Institute
Boston, Massachusetts
Conquer Cancer, the ASCO Foundation

Current Research

Goal: Investigating the mechanisms of therapeutic resistance and developing new approaches to overcome or prevent resistance in breast cancer patients.

Impact: Breast cancers that express the estrogen receptor (ER) can be targeted by endocrine therapy (ET). This is complicated by the fact that ER expression can change over time sometimes decreasing to such a low level that it is considered ER loss. One cause of resistance to ET is thought to be due to the loss of ER. Dr. Abravanel and his team are investigating the loss of estrogen receptor (ER) expression as a mechanism of resistance in MBC patients.

What’s next: They will characterize the samples that demonstrate ER loss by performing detailed sequencing to determine the alterations that cause ER loss and to identify the drivers of tumor progression following ER loss. 

Metastatic breast cancer (MBC) remains incurable, even with modern therapies, largely because it develops resistance in nearly all cases. Breast cancer tumors that express the estrogen receptor (ER) can be targeted by endocrine therapy (ET). Resistance to ET develops in some cases due to the decrease of ER in tumors over the course of treatment. Dr. Abravanel and his team are investigating the loss of estrogen receptor (ER) expression as a mechanism of resistance in MBC patients.

Full Research Summary

Research area: Investigating the mechanisms of therapeutic resistance and developing new approaches to overcome or prevent resistance in breast cancer patients.

Impact: While progress in screening and drug development have led to meaningful improvements in survival, breast cancer remains a leading cause of death among women. This is largely because metastatic breast cancer (MBC) remains incurable, even with modern therapies,largely due to the development of resistance in nearly all cases. Many breast cancers express estrogen receptor (ER) which can be targeted by endocrine therapy (ET). However, resistance to ET develops and is complicated by several potential causes - one of which is loss of ER. ER loss is estimated to occur in approximately 20 percent of cases with these patients experiencing worse outcomes as compared to those whose tumors retain ER. Dr. Abravanel and his team are investigating the loss of estrogen receptor (ER) expression as a mechanism of resistance in MBC patients. He and his team are focusing directly on biopsies from MBC patients to study ER loss and hopes to develop novel approaches to treating patients with MBC.
 
Current research: As part of his Conquer Cancer study, supported by BCRF, Dr. Abranavel is uncovering the biologic underpinnings of ER loss in MBC tumors by characterizing the tumor samples that demonstrate ER loss and identifying factors involved in the development of therapeutic resistance. Recognizing the importance of performing biopsies in patients with MBC, his team has collected hundreds of biopsies from patients with MBC to provide valuable information for research and clinical purposes. They have identified samples that demonstrate ER loss and will therefore be important to advance our understanding of ET resistance in MBC. Dr. Abranavel and his team will characterize these samples and perform detailed sequencing to determine the alterations that cause ER loss and to identify the drivers of tumor progression following ER loss. These studies have significant long‐term potential for development of therapeutic approaches that will impact the care of patients with MBC.

Biography

Daniel Abravanel, MD, PhD is currently a fellow in medical oncology at Dana‐Farber Cancer Institute. He received his undergraduate degree from Duke University and received an MD/PhD through the Medical Scientist Training Program at the University of Pennsylvania. He went on to complete his residency in internal medicine at Brigham and Women’s Hospital. Dr. Abravanel’s clinical and research efforts are focused on elucidating the mechanisms of therapeutic resistance in breast cancer patients. He hopes to apply his findings to develop new approaches to overcome or prevent drug resistance.

BCRF Investigator Since

2020

Area(s) of Focus