Fox Chase Cancer Center Researchers Identify Mechanism for Drug Resistance in Ovarian Cancer

James Duncan, PhD
James Duncan, PhD
PHILADELPHIA (July 27, 2016) – Researchers at Fox Chase Cancer Center have found that BET inhibitors, drugs that block the function of BET bromodomain proteins in cancer cells, may have limited success as single agents in ovarian cancer due to reprogramming of the protein kinome, leading to drug resistance.

The laboratory work, published in Cell Reports, showed that ovarian cancer cells could bypass BET inhibitor therapies by activating networks of protein kinases, and that a combined therapeutic approach targeting these kinases will likely be needed to prevent drug resistance.

“Small-molecule BET inhibitors are actively being pursued in clinical trials for a variety of cancers as part of a push toward precision medicine. This study sought to determine what might lead to resistance in ovarian cancer,” said James Duncan, PhD, an Assistant Professor at Fox Chase in the Cancer Signaling and Epigenetics  Research Program.

For the current study, researchers used a mass spectrometry-based method that globally measured protein kinase signaling in a panel of ovarian cancer cell lines following BET inhibitor therapy. They found that the cells became resistant to the BET inhibitor treatment due to increased activity of a protein kinase network involved in cancer cell survival.

The researchers speculate that combining BET inhibitors with other agents targeting protein kinases might make them more effective in treating cancer.

This study is the first published from Fox Chase Cancer Center’s Cancer Kinome Initiative (CKI), which was funded in part by a generous grant from Donald E. Morel Jr., former CEO of West Pharmaceuticals and current chair of the Fox Chase Cancer Center Foundation Board of Directors.

Fox Chase Cancer Center (Fox Chase), which includes the Institute for Cancer Research and the American Oncologic Hospital and is a part of Temple Health, is one of the leading comprehensive cancer centers in the United States. Founded in 1904 in Philadelphia as one of the nation’s first cancer hospitals, Fox Chase was also among the first institutions to be designated a National Cancer Institute Comprehensive Cancer Center in 1974. Fox Chase is also one of just 10 members of the Alliance of Dedicated Cancer Centers. Fox Chase researchers have won the highest awards in their fields, including two Nobel Prizes. Fox Chase physicians are also routinely recognized in national rankings, and the Center’s nursing program has received the Magnet recognition for excellence six consecutive times. Today, Fox Chase conducts a broad array of nationally competitive basic, translational, and clinical research, with special programs in cancer prevention, detection, survivorship, and community outreach. It is the policy of Fox Chase Cancer Center that there shall be no exclusion from, or participation in, and no one denied the benefits of, the delivery of quality medical care on the basis of race, ethnicity, religion, sexual orientation, gender, gender identity/expression, disability, age, ancestry, color, national origin, physical ability, level of education, or source of payment.

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