Assistant Professor, Medicine (Oncology)
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. McDaid and Horwitz 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. Hayley McDaid received her PhD from the Queens University of Belfast, where she characterized the role of the cAMP-dependent protein kinase A signaling pathway in breast and ovarian cancer. These studies pioneered her present-day interest in targeted therapies, pharmacogenomics and rationally designed drug combinations.
Dr. McDaid's broad research theme in breast cancer is focused on investigating molecular mechanisms of action and resistance to novel therapeutics. She is interested in defining the ‘circuitry’ of breast cancer in the different molecular subtypes of triple negative tumors; and mechanisms by which tumors counteract the effects of therapy. As part of this focus, Dr. McDaid has been studying chemotherapy-mediated senescence, a type of growth arrest that is increasingly perceived as a deleterious outcome of treatment. Together with colleagues, she is interested in chemical-biological approaches to minimize the risk of developing senescence during treatment.