ChristianaCare cancer specialists aid in discovery suppressing chemotherapy-resistant ovarian cancer

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Gynecologic oncologists at the Helen F. Graham Cancer Center & Research Institute collaborated with research scientists at The Wistar Institute on a new strategy to suppress the growth of cancer stem cell-like cells that can cause cancer relapse after treatment for epithelial ovarian cancer.

Their findings, published online in Cancer Research, offer a potential solution to the major challenge of chemoresistance to platinum-based drugs that remain the standard of care for this disease.

Stephanie Jean, M.D., Mark G. Cadungog, M.D., and Mark E. Borowsky, M.D., worked with scientists at The Wistar Institute to study how the body’s immune system can be trained to attack cancer without harming healthy cells.

Epithelial ovarian cancer is the most common form of ovarian cancer and the leading cause of gynecologic cancer deaths in the United States. Chemoresistance to platinum-based drugs like cisplatin represents a major treatment challenge, as more than 50% of affected women ultimately relapse and die from this disease.

The Wistar researchers demonstrated that NAMPT, an enzyme critical for NAD+ biosynthesis, drives the activation of stem-like chemoresistant cells following cisplatin treatment. Researchers showed that a combination of cisplatin treatment with pharmacological inhibition of NAMPT suppressed the outgrowth of resistant cancer cells in the laboratory and prolonged disease-free survival in a preclinical model.

Rugang Zhang, Ph.D.

“Based on previous findings from our laboratory, we have identified a molecule that can be pharmacologically blocked to get rid of resistant cells while preserving the beneficial anticancer power of cisplatin, which still remains the standard of care for this disease,” said Rugang Zhang, Ph.D., deputy director of The Wistar Institute Cancer Center, professor and co-program leader of the Gene Expression and Regulation Program, and senior author on the paper.

ChristianaCare’s Mark Borowsky, M.D., division director of Gynecologic Oncology at the Graham Cancer Center, joined gynecologic oncologists Mark Cadungog, M.D., director of Robotic Surgery, and Stephanie Jean, M.D., director of Gynecologic Oncology Research, as co-authors on the Wistar study.

“Molecular biology and targeted therapy are the future of cancer care,” said Dr. Borowsky. “We hope our continuing collaboration with our research partners at Wistar will bring dramatic improvements for our patients on those therapies.”

Nicholas Petrelli, M.D., Bank of America endowed medical director of the Helen F. Graham Cancer Center & Research Institute, and Dario C. Altieri, M.D., president and CEO of The Wistar Institute and director of the Wistar Institute Cancer Center.

“The collaboration with Dr. Zhang and The Wistar Institute Cancer Center is one of many successful partnerships between Wistar scientists and our oncology teams working toward more effective therapies not only for patients at the Graham Cancer Center but everywhere,” said Nicholas Petrelli, M.D., Bank of America endowed medical director.

“In addition to providing high quality, viable tissue samples for Wistar research studies, our clinicians actively participate in concept development, sharing their unique understanding of the everyday patient experience,” Dr. Petrelli said.

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