BRCA1 Mutations Influence Therapy Resistance Mechanisms in Breast and Ovarian Cancers

PHILADELPHIA (September 25, 2018)— In addition to impacting cancer risk, mutations in the BRCA1 gene also have a role in determining whether a patient responds to certain types of therapies. In a new publication, Neil Johnson, PhD, an assistant professor in the Molecular Therapeutics Program at Fox Chase Cancer Center, found that cancers with different types of BRCA1 mutations have varying susceptibilities to biological pathways that induce resistance to PARP inhibitors, an emerging class of cancer drugs. The paper appears in the journal Cell Reports.

“PARP inhibitor resistance is a challenge in treating cancers, and we report in this paper that a common mechanism of resistance may be more likely to arise in cancers with specific classes of BRCA1 mutations,” Johnson said. “BRCA1-mutant cancers that are less receptive to this resistance mechanism could have prolonged therapeutic benefit from PARP inhibitor treatments.”

Johnson said future research would be needed to assess potential relationships between specific BRCA1 mutations and particular PARP inhibitor resistance pathways in order to determine the best treatment course for each patient.

Presently, three PARP inhibitors are FDA-approved, and several others are being tested in clinical trials. Women with a BRCA1 mutation are about six times more likely to be diagnosed with breast cancer and more than 30 times more likely to be diagnosed with ovarian cancer.

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 five 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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