Findings from clinical study to be presented in talk at AACR annual meeting in Washington, D.C.
- Collaborative research reveals processes that lead to tamoxifen resistance
- Drug disrupts ‘stranglehold’ estrogen receptor puts on tumor suppressor p53
- Findings suggest opportunities to enhance tamoxifen’s effectiveness
BUFFALO, N.Y. — Tamoxifen is widely used for the treatment of women diagnosed with certain types of early and advanced breast cancers, but not all patients will benefit from it. A team from Roswell Park Comprehensive Cancer Center and Northwestern University examined the mechanisms behind tamoxifen resistance. Their findings are being presented today in a talk at the American Association for Cancer Research (AACR) Annual Meeting 2017, which continues through April 5 in Washington, D.C.
Gokul Das, PhD, Associate Professor of Oncology in the Department of Pharmacology & Therapeutics and Co-Director of the Breast Disease Site Research Group at Roswell Park, is the senior author and Swati Kulkarni, MD, of Northwestern University is first author of “Novel effect of tamoxifen therapy: disruption of ER-p53 interaction leading to altered gene expression profile in human breast tumors” (abstract CT012), to be presented as part of the Clinical Trials Minisymposium on Sunday, April 2 at 3 p.m. EDT.
Dr. Das has previously reported that estrogen receptors, a type of major protein present in certain breast cancers, bind to the p53 tumor-suppressor gene and deactivate it. For this current research, a prospective clinical study, the team analyzed tumor samples from 53 breast cancer patients from Roswell Park and the University of Chicago Medicine Comprehensive Cancer Center.
The researchers report that the binding of estrogen receptors to the p53 suppressor gene is disrupted after four weeks of tamoxifen therapy. Tamoxifen is able to activate various anti-cancer genes or functions, thereby stimulating the antitumor activity of p53 in breast cancer cells.
“This study unravels a previously unknown capability of tamoxifen to disrupt the stranglehold of estrogen receptors over the p53 tumor-suppressor gene,” says Dr. Das. “This clinical study exemplifies how to develop an original idea, generate findings in the research laboratory and then apply those results to a clinical study in breast cancer patients, and may help us to identify patients who will most benefit from tamoxifen therapy. It also provides new insight into ways of exploiting p53 to repurpose tamoxifen therapy in combination with other agents for breast cancers that are usually not responsive to conventional tamoxifen therapy.”
This work was supported in part by a grant from the National Cancer Institute.
More than 25 teams from Roswell Park Comprehensive Cancer Center have been invited to present their research at the 2017 AACR annual meeting. These research studies run the gamut from findings that reveal novel insights about a potential biomarker for glioma to an epigenetic approach to understanding androgen deprivation therapy and a microRNA signature scoring system that may predict bone metastasis in breast cancer.
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The mission of Roswell Park Comprehensive Cancer Center is to understand, prevent and cure cancer. Founded in 1898, Roswell Park is one of the first cancer centers in the country to be named a National Cancer Institute-designated comprehensive cancer center and remains the only facility with this designation in Upstate New York. The Institute is a member of the prestigious National Comprehensive Cancer Network, an alliance of the nation’s leading cancer centers; maintains affiliate sites; and is a partner in national and international collaborative programs. For more information, visit www.roswellpark.org, call 1-877-ASK-Roswell Park (1-866-559-4838) or email AskRoswell@Roswellpark.org. Follow Roswell Park on Facebook and Twitter
Deborah Pettibone, Public Information Specialist
mobile 716-868-6182; deborah.pettibone@roswellpark.org