Raj Shah, a 5th year PhD Candidate, was recently selected as a recipient of the 2018-2019 Rutgers Pharmaceutical Research Travel Award, a program that has been generously made by Dr. Paul Kurtulik, an EMSOP alumni. Raj attended the 2019 Annual Meeting of the American Association for Cancer Research (AACR) in Atlanta, Georgia.
Raj’s research investigates the relationship between metabotropic glutamate receptor 1 (GRM1)–mediated signaling and altered glutamate bioavailability. GRM1-activated (GRM1+) melanomas exhibited significantly increased expression of glutaminase (GLS), a glutaminolytic enzyme that catalyzes the conversion of glutamine to glutamate before it enters the TCA cycle. In cultured GRM1+ melanoma cells, CB-839, a potent, selective, and orally bioavailable inhibitor of GLS, suppressed cell proliferation while riluzole, an inhibitor of glutamate release, promoted apoptotic cell death in vitro and in vivo. Combined treatment with CB-839 and riluzole treatment proved to be superior to single agent treatment, restricting glutamate bioavailability and leading to effective suppression of tumor cell proliferation in vitro. Most importantly, disruption of GRM1 signaling through combined actions of CB-839 and riluzole significantly suppressed tumor growth in two independent xenograft mouse models of melanoma, with no obvious symptoms of toxicity detected. These findings may contribute to the development of cancer therapeutics aimed at mitigating GRM1-induced metabolic alterations in cancer patients.
In Raj’s words, “The AACR conference provided a solid platform to share my research findings and gain valuable advice from experts in the field of cancer cell metabolism. Attending AACR enhanced my scientific knowledge, as I was educated on the latest developments from cancer specialists. The ultimate highlight of this trip was getting a chance to meet and converse with Dr. James Allison, the winner of the 2018 Nobel Prize for Physiology and Medicine for his discovery of enhancing immune function and utilize it as a therapy to combat cancer.”