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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 tumors become drug resistant.
- These studies may lead to targeted therapies and new combination approaches to counter drug resistance and improve outcomes for patients with aggressive breast cancer.
Triple negative breast cancer (TNBC) is an aggressive form of breast cancer. TNBC tumors are frequently resistant or become resistant to a variety of drugs, increasing their potential to spread to other tissues–a process called metastasis. Drs. Horwitz and McDaid are conducting laboratory studies to identify more effective and less toxic drugs for patients with TNBC.
Full Research Summary
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 team has made steady progress in identifying a series of molecules that are similar to the common chemotherapy drug Taxol but with a reduced risk of promoting therapy-mediated tumor dormancy.
Dormancy is a state in which cancer cells do not divide. They do however, produce vast quantities of inflammatory proteins that can make tumor cells migratory, leading to metastatic disease. Dormant cells are frequently enriched in tumors following completion of chemotherapy, implying an association with therapeutic resistance.
Drs. McDaid and Horwitz will thus rank potential drug candidates on their ability to strongly induce tumor cell death coupled with low risk of inducing dormancy. These efforts may lead to the development of a novel chemotherapy drug with potent tumor cell killing activity in TNBC.
Complementing this work, they are also studying how tumor 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.