Targeting the endocannabinoid system as a novel anti-cancer therapy for urothelial carcinoma

Abstract

Urothelial carcinoma (UC) is the most common form of bladder cancer in both humans and dogs. Treatment options for UC often have variable response rates with only 50% of patients responding long term. Evidence suggests cannabinoids, both endogenous and plant based, are potent anti-cancer therapies with potential to enhance current treatments. However, their potential benefits have not been explored in UC. It was determined that cannabidiol (CBD), a phytocannabinoid, synergizes chemotherapy treatment. Further, combination with radiation therapy demonstrated CBD’s potential to radiosensitize UC cell lines. Finally, inhibition of MAGL, a metabolic enzyme in the endocannabidiome, impaired migration and invasion conferring a less aggressive phenotype. These findings suggest that cannabinoids may be novel anti-cancer therapies for both canine and human UC. Further studies are required to confirm these results in more complex models.