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Co-treatment of blood thinner, chemotherapy reduces ovarian cancer tumors, Lankenau Institute for Medical Research scientists discover

Lankenau Medical Center January 10, 2017 Research News

Their studies reveal new possibilities for therapeutic relevance to cancer, other inflammatory disorders

Chemotherapy to treat ovarian tumors can be improved through combination with a blood thinner, according to a recent preclinical study led by Main Line Health’s Lankenau Institute for Medical Research (LIMR) scientists Susan Gilmour, PhD, and Eric Alexander, PhD, as published recently in Oncotarget, a leading biomedical journal. The blood thinner used in the study, dabigatran etexilate (Pradaxa®), was pioneered in clinical trials several years ago at LIMR.

Cancer patients are at a markedly increased risk for developing blood clots, and chemotherapy exacerbates that risk. The researchers hypothesized that Pradaxa, combined with the widely used chemotherapy drug cisplatin, could cooperate to stop the growth of primary ovarian tumors and the development of malignant ascites, a fluid mix of tumor cells, growth factors and immune cells. Development of ascites is common in ovarian cancer patients, where this event is associated with poor prognosis and reduced quality of life, the researchers noted.

With a five-year survival rate of just 27 percent, ovarian cancer has the highest mortality rate worldwide of the gynecologic cancers. More than one third of ovarian cancer patients present with malignant ascites at diagnosis.

“Our studies showed that co-treatment with dabigatran etexilate and cisplatin not only inhibited ovarian tumor growth in mice, it also reduced the development of malignant ascites when compared to treatment with either therapy alone,” said Dr. Gilmour, who served as the Principal Investigator of the study. “These studies will provide important groundwork to extend the use of this new oral anti-coagulant in cancer patients, not only to treat their higher incidence of blood clots and pulmonary embolisms but also to hopefully inhibit tumor progression.”

Co-treatment impacts tumor microenvironment

The researchers found that the co-treatment modulated the tumor microenvironment in notable ways. It decreased certain types of cytokines, or molecular messengers, that promote tumor development. It also reduced the population of suppressor cells, which act to stop the immune system from recognizing and killing cancer cells, and it appears to activate T cells that can attack tumor cells.

“Of particular importance was the novel discovery that the anti-tumor effect of co-treatment was associated with dramatic immunomodulatory effects including decreased levels of proinflammatory cytokines, reduced immunosuppressive myeloid cell populations in the ascites, and a concomitant increase in CD8+ T cell antitumor activity,” wrote the study’s authors.

Their results indicate that a combined treatment of dabigatran etexilate and cisplatin may be a more effective treatment than either drug alone, and the authors called for safety and efficacy studies in humans to confirm the hypothesis.

Other LIMR authors of the study include biomedical research associates Allyson Minton and Molly Peters. Joanne van Ryn, PhD, of the German pharmaceutical company Boehringer Ingelheim Pharma GmbH & Co., also contributed to the research. Dr. Gilmour’s lab has received funding from Boehringer.

The study entitled “Thrombin inhibition and cisplatin block tumor progression in ovarian cancer by alleviating the immunosuppressive microenvironment” is available online in full.

LIMR’s role in Pradaxa’s developments

Beginning in 2006, LIMR served as the U.S. organizing site for the Phase III clinical trial of Pradaxa that eventually led to its registration with the U.S. Food and Drug Administration as a new drug entity in 2010. This international trial had three organizing sites and included approximately 18,000 patients worldwide, including about 5,000 patients in the United States coordinated through LIMR.

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.

The Main Line Health system 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 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, the Mid-Atlantic Alliance for Performance Excellence (MAAPE) Excellence Award, and recognition as among the nation’s best employers by Forbes magazine. 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.


Mary Kate Coghlan
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