Susan B. Horwitz, PhD
New York, New York
Distinguished Professor Emerita
Department of Molecular Pharmacology
Rose C. Falkenstein Chair in Cancer Research
Albert Einstein College of Medicine
New York, New York
Identifying targeted therapies and novel combination approaches to decrease drug resistance and improve outcomes for patients with triple-negative breast cancer.
Therapeutics such as Taxol are indicated for first-line treatment of patients with triple-negative breast cancer (TNBC) and other types of breast cancer. While many patients experience good outcomes to this treatment, some patients are resistant to therapy or have an incomplete response, eventually relapsing after a period of remission. In addition, some patients develop toxicities or experience long-term, debilitating side effects. The BCRF research led by Drs. Horwitz and McDaid is focused on defining the fate of cancer cells that survive anti-cancer therapy, specifically investigating the causes of resistance to drugs like Taxol. They have synthesized novel molecules that work like Taxol but are more effective at killing breast cancer cells in laboratory models. They are investigating the therapeutic efficacy of these molecules with the long-term goal of developing potent, less toxic Taxol-like drugs for use in advanced disease.
One of the synthesized drugs has shown promising anti-tumor efficacy and a low toxicity profile and they are now evaluating its mechanism of action. In other studies, they are examining cellular senescence—an underlying cause of relapse after chemotherapy. They showed that while senescent cancer cells are damaged and do not divide, they do produce inflammatory proteins that can promote the growth of neighboring non-damaged tumor cells thereby leading to treatment resistance, recurrence, or metastasis.
The team will continue investigating potential drug candidates for treatment of TNBC that both strongly induce tumor cell death and have a low risk of inducing cellular dormancy. In addition, they will delineate the molecular signatures of senescence that can be exploited to develop new drugs to eradicate these tumor cells.
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 discovered Taxol— a drug isolated from the yew plant, Taxus brevifolia—which has been a major focus of their work and, today, 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—this work 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.
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