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Innovative approach to ovarian cancer treatment unveiled by biomedical scientists at the Lankenau Institute for Medical Research

March 8, 2016 Research News

A new precision medicine approach to treat the most aggressive forms of ovarian cancer was recently announced by a consortium of researchers led by Janet Sawicki, PhD, and her colleagues at the Main Line Health’s Lankenau Institute for Medical Research (LIMR).

The ground-breaking study is the first to show the potential of targeted reduction of a specific protein in ovarian tumors, but not in healthy cells, following systemic administration. Targeting was achieved using a novel nanocarrier bound to a molecule that directs uptake of a therapeutic to tumor cells. In preclinical studies, tumor growth was suppressed and life span was significantly extended in animals treated with the new therapy.

“We have shown that suppression of a protein called HuR, a master regulator of hundreds of genes, disrupts multiple essential cellular molecular pathways needed by ovarian tumor cells to survive, a finding that sets this therapeutic approach apart from other therapies that target a single gene,” said Dr. Janet Sawicki, professor and deputy director of LIMR, and a leading researcher of the consortium. “Small interfering RNA [siRNA], a molecular technology developed over 10 years ago, can effectively inhibit the function of a single gene of interest. Targeted delivery of siRNA to tumors via systemic administration has been a major challenge that, to date, has impeded the advancement of promising siRNA-based therapies to the clinic. Our research team has developed a nanocarrier that meets this challenge and targets an HuR-inhibitory siRNA to ovarian tumors.”

Need for more treatment options

In the United States, ovarian cancer is the second most common gynecologic cancer. This year, an estimated 22,000 American women will be diagnosed, and about 14,000 women a year die of the disease, according to the American Cancer Society. In fact, ovarian cancer is the fifth most common cause of cancer-related death in women. The standard treatment for patients with advanced-stage ovarian cancer is removal of the ovaries, followed by chemotherapy. While 80 percent of these patients initially have good results, tumors in most patients eventually return, and the recurrent tumors develop resistance to chemotherapy. A more effective treatment option is needed.

The consortium’s study was published in a recent edition of Cancer Research, a journal of the American Association for Cancer Research. The LIMR researchers teamed up with scientists at Genisphere LLC, a biotech company in Hatfield, Pa., to use their DNA nanocarrier platform technology, called 3DNA®, for targeted siHuR delivery. The results showed that the tumor growth rate in treated mice was greatly reduced, while no toxicity to healthy cells was observed.

“This work takes a significant step forward in the field of cancer siRNA therapeutics and advances the potential use of 3DNA technology in the clinic,” stated Dr. Sawicki, a cancer biologist whose long-standing research objective has been to develop an effective therapy for metastatic cancer.

Other LIMR-affiliated members of the research team include Yu-Hung Huang, a Drexel University graduate student; Weidan Peng, PhD, research assistant professor; and Narumi Furuuchi, biomedical research assistant. LIMR is part of the Lankenau Medical Center.

The consortium also included scientists from Thomas Jefferson University’s Department of Surgery; the Max Delbruck Center for Molecular Medicine in Berlin, Germany; and Seattle-based NanoString Technologies, a provider of life science tools. Their work was funded in part by grants from private foundations, including the Marsha Rivkin Center for Ovarian Cancer Research, the Sharpe-Strumia Research Foundation of Bryn Mawr Hospital, and the Sarah Parvin Foundation.

About Main Line Health

Founded in 1985,Main Line Health is a not-for-profit health system serving portions of Philadelphia and its western suburbs. Main Line Health’s commitment—to deliver advanced medicine to treat and cure disease while also playing an important role in prevention and disease management as well as training physicians and other health care providers—reflects our intent to keep our community and ourselves well ahead. A team of more than 10,000 employees and 2,000 physicians care for patients throughout the Main Line Health system.

At Main Line Health’s core are four of the region’s most respected acute care hospitals—Lankenau Medical Center, Bryn Mawr Hospital, Paoli Hospital and Riddle Hospital—as well as one of the nation’s recognized facilities for rehabilitative medicine, Bryn Mawr Rehabilitation Hospital.

Main Line Health also includes Mirmont Treatment Center for drug and alcohol recovery; Main Line Health HomeCare & Hospice, which includes skilled home health care, hospice and home infusion services; Main Line Health Centers, primary and specialty care, lab and radiology, and other outpatient services located in Broomall, Collegeville, Concordville, Exton, King of Prussia and Newtown Square; Lankenau Institute for Medical Research, a biomedical research organization; and Main Line HealthCare,one of the region’s largest multispecialty physician networks.

Main Line Health is the recipient of numerous awards for quality care and service, including System Magnet® designation, the nation’s highest distinction for nursing excellence and the Mid-Atlantic Alliance for Performance Excellence (MAAPE) Excellence Award. Main Line Health is committed to creating an environment of diversity, respect and inclusion and has proudly embraced the American Hospital Association’s #123forEquity Pledge to Act to eliminate disparities in care. We are dedicated to advancing patient-centered care, education and research to help our community stay healthy.

About Lankenau Institute for Medical Research

Lankenau Institute for Medical Research (LIMR) is a nonprofit biomedical research institute located on the campus of Lankenau Medical Center and is part of Main Line Health. Founded in 1927, LIMR’s mission is to improve human health and well-being. Faculty and staff are devoted to advancing innovative new approaches to formidable medical challenges, including cancer, cardiovascular disease, gastrointestinal disorders and autoimmune diseases, such as diabetes and arthritis. LIMR’s principal investigators conduct basic, preclinical and translational research, using their findings to explore ways to improve disease detection, diagnosis, treatment and prevention. They are committed to extending the boundaries of human health through technology transfer and training of the next generation of scientists and physicians.