Titles and Affiliations

Associate Professor, Department of Medicine/Oncology
Associate Professor, Department of Molecular Pharmacology

Research area

Identifying targeted therapies and novel combination approaches to decrease drug resistance and improve outcomes for patients with triple-negative breast cancer.

Impact

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 Dr. McDaid is focused on defining the fate of cancer cells that survive anti-cancer therapy, specifically investigating the causes of resistance after therapy with 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.  

Progress Thus Far

One of the candidate drugs has shown promising anti-tumor efficacy and a low toxicity profile and Dr. McDaid’s team is now evaluating its mechanism of action. In the last year, they demonstrated it has distinct structural differences compared to taxol and this may account for its unique properties.  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. Dr. McDaid also examined the changes in senescence-associated proteins and found that they decreased upon treatment with the candidate drugs.  

What’s next

Dr. McDaid 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. Her team will also investigate the mechanism of action of these candidate drugs and continue to delineate the molecular signatures of senescence that can be exploited to develop new drugs to eradicate these tumor cells. 

Biography

Hayley McDaid, PhD received her degree 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. With her colleagues, she is interested in defining chemical-biological approaches to minimize the risk of developing senescence during treatment.

BCRF Investigator Since

2008

Donor Recognition

The David Yurman Award

Areas of Focus