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Susan B. Horwitz , PhD
Distinguished University Professor
Albert Einstein College of Medicine
Bronx, New York
Seeking to identify new therapeutic options for triple negative and BRCA-driven breast cancers.
Laboratory studies are ongoing to test new drug candidates in models of triple negative breast cancer and to understand how tumor secreted proteins promote drug resistance.
These studies may lead to targeted therapies and new combination approaches to counter drug resistance and improve outcomes for breast cancer patients with aggressive disease.
Triple negative breast cancer (TNBC) comprises approximately 15-20 percent of all breast cancers. These aggressive tumors are treated with a cocktail of chemotherapy drugs. Although many patients have excellent survival following treatment, some patients with specific types of TNBC have an incomplete response, and/or relapse after a period of remission. In particular, patients who have hereditary gene mutations in pathways that control DNA damage, such as BRCA, often have a high risk of relapse following treatment.
To address these challenges, Drs. Horwitz and McDaid have screened novel chemotherapy drugs against TNBC cells to identify those with superior activity and less toxicity than conventional therapy. The optimal drug candidates will not induce tumor cell dormancy, or senescence, a common effect of chemotherapy that leads to drug resistance and recurrence.
Senescent cancer cells produce vast quantities of inflammatory proteins that can make other tumor cells migratory. So while they lay sleeping, they are aiding the development of metastatic disease.
To date, the research team has identified two promising candidates. One is very effective in triple negative breast cancer cells that have mutations in BRCA genes. The researchers continue to optimize the anti-cancer efficacy of lead compounds in laboratory models of aggressive disease.
Complementing this work, they are also studying how proteins secreted from cancer cells interact with immune cells to promote a chemo resistant tumor microenvironment and enhance cancer cell survival. They have identified a component of the cytoskeleton (the cellular scaffolding) that facilitates transport of these proteins and have shown that this process is overactive in cancer cells, and may be therapeutically targetable.
Future studies will elucidate the relevance of this transport mechanism to cancer cell survival by generating TNBC cell lines that are missing the transport protein.
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.