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 (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, drug-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 them in the laboratory and interrogate them at different stages of patient treatment. These CTC cultures provide the unique ability to better understand how breast cancer becomes resistant to therapy and identify druggable vulnerabilities, with the goal of suppressing breast cancer metastasis.

Progress Thus Far

The team is focused on two complementary strategies to address and combat these resistant cells. First, they are developing a new test to predict the likelihood of response to novel antibody-drug conjugates (ADCs), which represent one of the most promising developments in targeted treatment for drug-resistant cancer cells. Dr. Haber and his team are using cultured CTCs to assess whether cancer cells contain the antibody target before and during treatment with a corresponding ADC. These studies have the potential to non-invasively guide and monitor effective cancer treatments in patients with metastatic breast cancer.

Secondly, the team is employing state-of-the-art genome editing technology and genetic screens in cultures of CTCs to identify novel vulnerabilities and exploit them with established potent chemotherapy drugs. Recently, they have discovered that advanced breast cancer cells can change their biological features much more rapidly than early-stage cancer cells, partly explaining how fast they can develop drug resistance.

What’s Next

The team anticipates that the results derived from this research will provide a new strategy for selecting and monitoring treatments for patients with metastatic breast cancer undergoing ADC therapy. The team plans to follow up these results by extending diagnostic studies to larger groups of patients receiving different ADCs. Additionally, the research will provide insights into novel drug targets in advanced breast cancer. Success in either of these areas could significantly impact treatment strategies for patients with advanced breast cancer.