New Drug Target, Companion Prognostic Test for Hormone Therapy–resistant Breast Cancer
A team of international cancer researchers led by Mathieu Lupien, PhD, at the Princess Margaret Cancer Centre, University Health Network, has identified the signaling pathway that is overactivated in estrogen receptor (ER)–positive breast cancer cells that are resistant to hormone therapies such as tamoxifen, aromatase inhibitors, or fulvestrant (Faslodex).
Resistance to hormone therapy is reported in almost half of ER-positive breast cancer patients, and no cure is currently available. The fact that the pathway, called Notch, is a drug target creates hope for a new therapy.
New Therapeutic Target
The findings, published online in the Proceedings of the National Academy of Sciences, “provide a new therapeutic target against hormone therapy–resistant breast cancers and a companion test to identify tumors that would become resistant” says Dr. Lupien, a scientist at the Ontario Cancer Institute, the research arm of the cancer center, and an Assistant Professor in the Department of Medial Biophysics, University of Toronto.
“In studying the epigenetics of hormone therapy resistance, we discovered that breast cancer cells behave like a chameleon,” says Dr. Lupien. “Indeed, as the chameleon changes its skin color to camouflage itself and evade predators, breast cancer cells change the appearance of their DNA through epigenetics to evade, in this case, hormone therapy.” In doing so, hormone therapy–resistant breast cancer cells highlight regions of their DNA related to the Notch pathway.
At the molecular level, the research team characterized the epigenetic appearances of the DNA of drug-resistant and drug-responsive breast cancer cells. The team discovered that the Notch signaling pathway plays the predominant role in drug-resistant breast cancer cells even if cells remain positive for ER.
Next Steps
“This is a highly promising discovery that could rapidly translate in the clinic. Drugs against the Notch pathway are available,” says Dr. Lupien. The key will be to test the efficacy of these drugs against hormone therapy resistance in breast cancer.
The research was funded by the National Cancer Institute, the American Cancer Society and the Ontario Institute for Cancer Research. Dr. Lupien’s research is also supported by The Princess Margaret Cancer Foundation.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
