(Wynnewood, Pa, March 25, 2016) – 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, Ph.D., 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, Ph.D., 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.
Genisphere LLC is the provider of the 3DNA® platform for targeted drug delivery. 3DNA® is a nanoscale, multivalent scaffold made from proprietary, synthetic DNA formed in a flexible, branched structure. 3DNA® nanocarriers are engineered and cross-linked to form a stable architecture while maintaining the biocompatibility of the nucleic-acid building blocks, and demonstrate efficacy and safety with a variety of drug cargos across multiple indications. Genisphere’s technology is IP-protected and fully customizable to deliver small molecules, biologics, and nucleic acids with precise specificity enabled by multivalent targeting via antibodies, peptides and other molecular entities. Genisphere leverages a collaborative model to advance its 3DNA® drug delivery platform, and seeks additional partnerships with biotechnology and pharmaceutical companies to improve efficacy and reduce toxicity. Genisphere is also advancing its own lead compounds based on 3DNA® nanotechnology. For more information, please visit https://genisphere.com.
About Lankenau Institute for Medical Research
Founded in 1927, the Lankenau Institute for Medical Research (LIMR) is an independent, nonprofit biomedical research center located in suburban Philadelphia on the campus of Lankenau Medical Center. Part of Main Line Health, LIMR is one of the few freestanding, hospital-associated medical research centers in the nation. The faculty and staff at the Institute are dedicated to advancing an understanding of the causes of cancer, heart disease, diabetes and other illnesses. This information is used to help improve diagnosis and treatment of these diseases, as well as find ways to prevent them. LIMR is also committed to extending the boundaries of human health and well-being through technology development and the training of the next generation of scientists and physicians. To learn about LIMR, visit limr.org.