ALS Treatment, Riluzole, Shows Promise in Treating Advanced Prostate Cancer, Study Says

ALS Treatment, Riluzole, Shows Promise in Treating Advanced Prostate Cancer, Study Says
An approved treatment for amyotrophic lateral sclerosis (ALS), called riluzole, may be an effective option for people with aggressive prostate cancer because of its ability to induce androgen receptor degradation, according to a study. The study, “Riluzole induces AR degradation via endoplasmic reticulum stress pathway in androgen‐dependent and castration‐resistant prostate cancer cells” was published in the journal The Prostate. The relationship between prostate cancer and androgen is well-known, and many treatments against this disease focus on the direct inhibition of the androgen receptor, a molecule that activates prostate cancer-related genes. Androgen deprivation therapies, which directly target the androgen receptor, are the mainstay of advanced prostate cancer treatment. But despite initial responses, almost all patients progress to castration-resistant prostate cancer (CRPC) — an aggressive cancer that keeps growing even with low levels of testosterone, the major androgen in men. A strategy that cells use to create resistance is to produce variants (mutants or splice variants) of the androgen receptor that are not recognized by the common inhibitors. New medicatio
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  1. Riluzole induces AR degradation via endoplasmic reticulum stress pathway in androgen-dependent and castration-resistant prostate cancer cells. “The Prostate, Oct 2018 DOI: 10.1002/pros.23719”

    Prostate cancer (PCa) is the most common non-skin cancer among men in the United States and Western World. Androgen receptor (AR) plays a central role in normal development of the prostate gland, in prostate carcinogenesis and its progression to advanced metastatic and/or castration-recurrent state (CR-PCa). Functional AR proteins exist due to overexpression of wild-type AR, mutated-ARs, and ligand-independent AR-splice variants (e.g., AR-V7) and drive multiple mechanisms of resistance to both first- and second-generation androgen deprivation therapy (ADT). It is not surprising that AR protein degradation is under intense clinical investigation as a treatment strategy for metastatic and CR-PCa. Investigators have discovered that Riluzole (Rilutek), a well-tolerated FDA-approved oral medicine that has been routinely prescribed for the treatment of amyotrophic lateral sclerosis (ALS) significantly promotes degradation of wild-type and mutated ARs and AR-V7 through a distinct metabolic pathway in androgen dependent, castration recurrent, and enzalutamide-resistant PCa cells. The findings suggest that Riluzole should be investigated clinically for PCa treatment and strongly predict that it may be effective for both early stage and advanced disease”.
    Corresponing Author: Shahriar Koochekpour, M.D., Ph.D. of Roswell Park Comprehensive Cancer Center, Buffalo, New York, NY 14263

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