Research by investigators at The Cancer Institute of New Jersey (CINJ) is showing new promise in the treatment of melanoma, the most serious of skin cancers. The findings, published in the May 27, 2010, online edition of the Journal of Investigative Dermatology further validate the team’s clinical and pre-clinical findings that blocking the signaling normally activated by a receptor called Grm1 results in decreased cell growth and decreased migration of melanoma cells, confirming that Grm1 is a potential target for the treatment of melanoma. The new studies continue to focus on a drug called riluzole, which is commonly used to treat Lou Gehrig’s disease (ALS). CINJ is a Center of Excellence of UMDNJ-Robert Wood Johnson Medical School.
Melanoma cells often produce the protein Grm1, which is normally produced in the central nervous system of mammals. Activation of this protein on the surface of melanoma cells increases growth and spread of disease. Riluzole, which is approved by the United States Food and Drug Administration for the treatment of ALS (a disease that affects nerve cells in the brain and spinal cord), has been shown to block Grm1’s action. This study, The Glutamate Release Inhibitor Riluzole Decreases Migration, Invasion, and Proliferation of Melanoma Cells, takes a closer look at key pathways which are critical for Grm1 to send messages that initiate melanoma growth and spread and examines the role riluzole and another similar drug play in blocking those messages. The work is based on that of the laboratory of Suzie Chen, CINJ member and professor of chemical biology at the Ernest Mario School of Pharmacy at Rutgers, the State University of New Jersey.
Previous studies by this team have shown that by blocking Grm1’s signaling action, the activation of two different pathways (MAPK and PI3K/AKT) important for melanoma cell development, growth, and spread, becomes suppressed. In this study, the investigators focused on riluzole and the experimental agent BAY 36-7620 and the functional consequences of blocking the signaling along these pathways with these agents. They were able to show that treatment of melanoma cells that produce Grm1 with riluzole or BAY 36-7620 have decreased signaling along these critical pathways, but also that this decrease in signaling results in a decrease in melanoma growth and spread, thus confirming the functional outcome of the observed decreased signaling.
James S. Goydos, MD, director of the Melanoma and Soft Tissue Oncology Program at CINJ and associate professor of surgery at UMDNJ-Robert Wood Johnson Medical School, is the study’s senior author. “We previously demonstrated that we could block the signals produced by Grm1 in melanoma cells. Now we have linked blocking of the signal with a decrease in growth, migration, and spread of melanoma, a critical step in validating Grm1 as a target for treating patients with melanoma. Because it is present in more than 60 percent of human melanomas, we have an appropriate ‘bull’s eye’ in Grm1, and riluzole is proving to be an effective arrow,” he stated. Dr. Goydos noted that targeting multiple pathways with new combination therapies involving riluzole would be ideal in producing the most effective melanoma treatments, based on their current studies.
SOURCE The Cancer Institute of New Jersey