Amyotrophic lateral sclerosis (ALS) drug boosts radiation effectiveness in melanoma models

A drug used to treat amyotrophic lateral sclerosis (ALS), commonly known as Lou Gehrig's disease, improved effectiveness of radiation therapy when administered to laboratory models with melanoma that metastasized to the brain, according to new research published in Pigment Cell & Melanoma Research (2015; doi: 10.1111pcmr.12327).

Melanoma, the deadliest of skin cancers, is often resistant to radiation therapy. To address this resistance, some melanoma treatment regimens may call for large doses of radiation. However, there is a risk of neurotoxicity when large doses are administered to the whole brain.

This work, conducted by researchers from Rutgers Cancer Institute of New Jersey and the Ernest Mario School of Pharmacy at Rutgers University in New Brunswick, New Jersey, examines radiation treatment when combined with the drug riluzole and its impact on melanoma that has spread to the brain.

Riluzole targets the protein GRM1, which is often abnormally produced by melanoma cells. Activation of this protein on the surface of melanoma cells increases growth and spread of the disease. Riluzole is approved by the US Food and Drug Administration for the treatment of ALS (a disease that affects nerve cells in the brain and spinal cord) and has been shown to block activation of the GRM1 protein.

In this current research, investigators used four sets of laboratory models affected with melanoma brain metastasis. One group was treated with the drug absorption vehicle dimethyl sulfoxide, while another was treated with dimethyl sulfoxide plus a weekly radiation dose of 4 Gy. A third group was treated daily with riluzole only, and the fourth received both daily riluzole and the weekly radiation dose of 4 Gy.

What they found was a decrease in tumor cell growth over a 37-day period when riluzole and radiation were combined as compared to those models that were given dimethyl sulfoxide only or riluzole alone or radiation alone.

“What this indicates is that riluzole sensitizes GRM1, helping these proteins act like a beacon for radiation so that only melanoma cells with the GRM1 protein will be targeted, sparing the rest of the brain and preserving the brain's functionality,” noted senior author, Suzie Chen, PhD, Cancer Institute member and professor of chemical biology at the Ernest Mario School of Pharmacy.

“With approximately 50% of patients with melanoma developing brain metastasis and fewer than 13% of those patients surviving 1 year or more, identifying new therapies for this population is paramount,” said coauthor James S. Goydos, MD, director of the Melanoma and Soft Tissue Oncology Program at the Cancer Institute and professor of surgery at Rutgers Robert Wood Johnson Medical School.

Goydos also noted their findings could have even broader implications. He added, “Because the GRM1 protein is also found in breast and prostate cancers, pretreatment with riluzole before radiation for these particular cancers might also result in the same outcomes.”

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