Daniel A. Haber, MD, PhD

Exploiting weaknesses in tumor cells to design cutting-edge treatments for advanced breast cancer.

Impact

The most common type of breast cancer, hormone receptor positive (HR-positive) breast cancer, is initially highly responsive to treatment. However, tumor cells can eventually become resistant to multiple courses of hormone therapy, and all too often, the cancer spreads and becomes unresponsive to all therapeutic options. To study advanced, resistant HR-positive breast cancer, Dr. Haber and his team use circulating tumor cells (CTCs), which are cancer cells caught in the bloodstream. These cells are very rare relative to blood cells, but the team has engineered highly sophisticated microfluidic devices that successfully capture CTCs. The tumor cells captured using this technology remain viable, and the team has been able to grow and study them in the laboratory, as well as potentially interrogate the cells at different stages of patient treatment. These cultures of advanced cancer cells provide the unique ability to better understand how breast cancer becomes resistant to therapy and identify vulnerabilities to exploit, with the goal of suppressing breast cancer metastasis.

What’s Next

The team is focused on two complementary strategies to address and combat breast cancer that becomes resistant to therapy. The team will study CTCs to determine whether they can predict response to novel antibody-drug conjugates (ADCs), with the goal of developing a strategy to match the correct therapy to the patient. The goal for this coming year will be to analyze blood samples from a group of women receiving ADC therapies for the presence of the protein targeted by the ADC drug, before and at intervals after their first treatment. The expectation is that the test will help predict which ADC drug is most appropriate for any given patient before beginning treatment, ascertain the depth and duration of drug response, and identify mechanisms of resistance when the ADC drug is no longer effective.
Secondly, the team is using state-of-the-art genome editing technology and genetic screens in long-term cultures of CTCs to identify and target novel pathways that allow cancer cells to persist despite this chemotherapy exposure, which ultimately gives rise to the resistant colonies of cells.
The team expects that the results derived from this research will provide a new strategy for treatment selection, and monitoring patients with metastatic breast cancer undergoing ADC therapy. Additionally, the research will provide insight into novel drug targets in advanced breast cancer.