Repurposing Food and Drug Administration-Approved Drugs to Promote Antitumor Immunity

Abstract

There has been a major resurgence of interest in immune-based approaches to treat cancer, based largely on the success of checkpoint inhibitors (anti-cytotoxic T-lymphocyte-associated antigen 4, anti-programmed cell death 1, and anti-programmed cell death ligand 1 antibodies) in several malignancies. However, not all tumors respond to checkpoint therapy, and there is clearly a need for additional approaches for enhancing tumor immunity. We summarize the critical elements necessary for mounting an efficacious T-cell response to a tumor. We cite drugs approved by the Food and Drug Administration for no-cancer indications that could be repurposed and used as part of an antitumor immune cocktail. We also list cancer drugs not initially intended to impact tumor immunity (soft repurposing) but that have been found to modulate the immune system. We highlight those drugs that might be used in combination with checkpoint inhibitors to increase response rates and survival of cancer patients. Our focus will be on drugs for which there are limited but existing human data. We cite supporting mechanistic mouse data as well. Repurposing drugs to modulate antitumor immunity is an opportunity to rapidly bring new, effective, and affordable treatments to cancer patients.