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Susan B. Horwitz, PhD
Distinguished University Professor
Albert Einstein College of Medicine
Bronx, New York
Goal: To identify new therapeutic options for triple negative and BRCA-driven breast cancers.
Impact: Drs. Horowitz and McDaid are testing new drugs that may overcome common drug resistance and cause fewer side effects than currently approved therapies, while also investigating the reasons underlying relapse after chemotherapy. Their work could lead to improved outcomes for patients with aggressive breast cancer.
What’s next: The team will continue to screen novel targeted anti-cancer therapies in triple negative breast cancer (TNBC). They also plan to develop biomarkers to accurately detect senescent tumor cells. Senescent – or dormant – tumor cells are often resistant to anti-cancer treatment and are known to drive cancer recurrence that leads to metastasis.
While many breast cancer patients have excellent survival following anti-cancer therapy, some patients are resistant to treatment or may have an incomplete response, leading to relapse after a period of remission. The BCRF research led by Drs. Horowitz and McDaid work is focused on defining the fate of cancer cells within a tumor population following therapy, especially those that are resistant to therapy. They are conducting laboratory studies to identify more effective and less toxic drugs for patients with TNBC and pursuing biomarkers of dormant tumor cells involved in metastasis and drug resistance.
Full Research Summary
Research goal: Identifying targeted therapies and new combination approaches to counter drug resistance and improve outcomes for patients with triple negative and BCRA-driven breast cancer.
Impact: While many patients with triple negative breast cancer (TNBC) respond well to therapy, others have an incomplete response and/or relapse after a period of remission. Those who have inherited mutations in genes that control DNA damage, such as BRCA, often have a particularly high risk of relapse following treatment. Drs. Horowitz and McDaid are investigating the causes of resistance to therapy and testing existing and novel drugs that could overcome it.
Current research: The team is currently focused on the role of tumor cell dormancy and the immune microenvironment on drug resistance and tumor cell survival.
What they’ve learned so far. Their studies have shown that dormant cancer cells produce inflammatory proteins that can promote metastasis and drug resistance. They have been screening novel molecules that target the tubulin cytoskeleton – the cellular “scaffolding” – for evidence of anti-cancer activity in TNBC.
What’s next: The team will continue investigating potential drug candidates for TNBC that both strongly induce tumor cell death and have a low risk of inducing cellular dormancy.
Dr. Susan Band Horwitz is a Distinguished University Professor at the Albert Einstein College of Medicine. She grew up in Boston and after graduating from Bryn Mawr College, received her PhD in Biochemistry from Brandeis University.
Dr. Horwitz has had a continuing interest in natural products as a source of new drugs for the treatment of cancer. Her laboratory has made Taxol, a drug isolated from the yew plant, Taxus brevifolia, a major focus of its work and today it is given to over a million patients. Dr. Horwitz' research played an important role in encouraging the development of Taxol by the National Cancer Institute.
Dr. Horwitz and her collaborators demonstrated that the effects of Taxol were due to a novel interaction between the drug and microtubules that identified Taxol as a prototype of a new class of anti-tumor drugs. Dr. Horwitz also has made significant contributions to our understanding of the molecular mechanisms underlying Taxol resistance in tumor cells.