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Lankenau Institute for Medical Research investigators develop novel therapy for melanoma tumors

January 16, 2018 Research News

A research team at the Lankenau Institute for Medical Research (LIMR), part of Main Line Health, has further characterized a cellular mutation that leads to a certain type of melanoma. Armed with that information, the team developed a novel treatment that, in preclinical studies, killed those particular melanoma tumor cells. An estimated 91,000 people in the United States will be diagnosed with melanoma in 2018, according to the American Cancer Society, and about 9,300 are expected to die from the disease this year. And while melanoma accounts for less than one percent of all skin cancer cases, it causes the vast majority of skin cancer deaths.

LIMR Professor Susan Gilmour, PhD, and her team found that the uptake of polyamines, small molecules that have been shown to promote the growth and survival of cancer cells, is elevated in melanoma tumor cells that express a mutant BRAF protein, a mutation that is found in over half of all melanoma tumors. The research team found that melanoma tumor cells harboring the mutant BRAF protein are more dependent on polyamine uptake for their survival, compared to normal cells or melanoma tumor cells with a wild type BRAF protein.

While currently available therapeutic agents that block the mutant BRAF protein are initially effective in treating most patients with mutant BRAF melanoma, the tumors grow back in almost 100 percent of patients within a few months. Dr. Gilmour and her team set out in their study to try to find a more effective treatment for those melanomas.

“We looked for an alternative approach to treating mutant BRAF melanoma, and we focused on another cellular pathway that the tumor cells need to survive,” said Dr. Gilmour. “Specifically, we found a way to target the transport system that brings polyamines into the tumor cells, thus cutting off the tumors’ life line.”

Gilmour’s team evaluated the sensitivity of mutant BRAF melanoma tumor cells to a novel aryl-polyamine (AP) drug, synthesized by Otto Phanstiel, PhD, a medicinal chemist at the University of Central Florida. Utilizing an innovative approach, the researchers used the polyamine transport system itself to successfully deliver the AP drug into tumor cells.

In preclinical studies they found that the AP drug preferentially entered and killed mutant BRAF melanoma cells compared to cells with a wild type or normal BRAF protein. Exploiting the dependence of mutant BRAF melanoma cells on polyamine uptake, the team discovered that co-treatment with their AP drug significantly boosted the sensitivity of mutant BRAF melanoma tumor cells to BRAF inhibitors, thus overcoming the resistance of mutant BRAF melanoma cells to a BRAF inhibitor.

Molly Peters and Allyson Minton in Dr. Gilmour’s lab contributed to the study whose results were published in the manuscript “A Novel Polyamine-Targeted Therapy for BRAF Mutant Melanoma Tumors” in a special issue on polyamines in the journal Medical Sciences. The full manuscript is available at mdpi.com.

This research is currently funded by a grant from the U.S. Department of Defense. Dr. Gilmour’s cancer research has also been funded for more than 25 years by grants from the National Institutes of Health.

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.