ALS Drug May Improve Outcomes for Those With Advanced Melanoma

A drug used to treat amyotrophic lateral sclerosis (ALS or Lou Gehrig's disease), is also helping to boost the effectiveness of radiation for those melanoma patients with metastasis to the brain.

Some cancers tend to be resistant to radiation treatment-including melanoma, so in order to address this issue, patients may be treated with large doses of radiation to the brain. If whole-brain radiation treatment is indicated, the risk of neurotoxicity increases.Researchers at Rutgers Cancer Institute of New Jersey and the Ernest Mario School of Pharmacy at Rutgers University took a closer look at a drug known as riluzole, which slows the progression of ALS. Riluzole targets a protein known as GRM1-a protein that is abnormally produced by melanoma cells. Activation of the GRM1 protein on the surface of melanoma cells increases growth and spread of the disease and riluzole has been shown to block activation of the GRM1 protein.

This study is published in the November issue of Pigment Cell & Melanoma Research.  

Researchers used four laboratory models affected with melanoma with metastasis to the brain. The first group was treated with a drug absorption vehicle known as dimethyl sulfoxide, while the second group was treated with dimethyl sulfoxide plus a weekly radiation dose of 4 Gy. The third group received riluzole only, while the forth group received daily riluzole and a weekly 4 Gy radiation dose. Investigators found that the forth group had a decrease in tumor cell growth over a 37-day period when both riluzole and weekly radiation was administered.

"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," notes senior author, Suzie Chen, PhD, Cancer Institute member and professor of chemical biology at the Ernest Mario School of Pharmacy.

Another author on the study, James Goydos, MD, director of the Melanoma and Soft Tissue Oncology Program at the Cancer Institute, notes that approximately 50% of patients with melanoma develop brain metastasis and fewer than 13% survive one year or more. "Identifying new therapies for this population is paramount,” said Goydos.

Targeting the GRM1 protein may not only benefit melanoma patients, but it may also benefit those patients diagnosed with breast and prostate cancers considering GRM1 is also found in both of these cancers as well.