The mechanism by which small cellular vesicles promote melanoma metastasis (spread of disease), will be further explored by investigators at Rutgers Cancer Institute of New Jersey and the Ernest Mario School of Pharmacy at Rutgers University.A recently awarded $200,000 grant (R21CA185835) from the National Cancer Institute to researchers Suzie Chen, Ph.D., and James S. Goydos, M.D., FACS, will support the work.
Melanoma, the deadliest of all skin cancers, remains one of the most challenging cancers to treat.While there have been recent advances with therapies that target specific mutations in melanoma, low response rates and development of secondary tumors highlight a need for new treatment approaches for this population. Previous work by Drs. Chen and Goydos on the abnormal expression of a neuronal receptor protein known as metabotropic glutamate receptor one (GRM1) in a large number of human melanoma cell lines and biopsy samples suggests it is likely involved in the development of melanoma. If activated on the cell surface, GRM1 has been found to increase melanoma growth and spread. Investigators aim to build upon their findings by examining the dependence of melanoma cells on the activated GRM1 protein to produce small vesicles within the cell known as exosomes. Exosomes have been proposed as a communication vehicle between melanoma cells and the surrounding tumor environment. The goal is to characterize the mechanism by which these exosomes are formed and how they contribute to melanoma metastasis.
“By elucidating the mechanism behind these exosomes, we are further building on our knowledge of GRM1 which is critical in helping to identify new anti-cancer therapies for melanoma patients,” notes Dr. Chen, Cancer Institute member and professor of chemical biology at the Ernest Mario School of Pharmacy.
The new work also will examine preand post-treatment clinical samples from three different clinical trials that explored the effects of the drug riluzole — a treatment commonly given to patients with Lou Gehrig’s disease that is found to block activation of the GRM1 protein.The goal is to search for a possible correlation between exosome production and biologic response in patients with melanoma.
“The spread of melanoma typically leaves patients with a poor prognosis. Combined with the progress we have seen in clinical trials examining the effects of riluzole in melanoma patients, further knowledge of exosomes and the role they play in melanoma metastasis will help us shape future studies,” adds Dr. Goydos, director of the Melanoma and Soft Tissue Oncology Program at the Cancer Institute and professor of surgery at Rutgers Robert Wood Johnson Medical School.
The grant will support the work through 2016. For more information, visit www.cinj.org.