Nitric Oxide and Platinum-Derivative-Based Regimens for Cancer Treatment: From Preclinical Studies to Clinical Trials

Chemoresistance to platinum-based antitumor agents remains a major hindrance faced by patients with a wide variety of solid tumors. New effective strategies are still needed to improve chemosensitization and overcome chemoresistance of tumors by platinum-based chemotherapies. Over the past decade, considerable knowledge on the antitumor effect of nitric oxide (NO) and its mechanisms of action has been gained. Here, we provide an overview of the basic mechanisms of resistance to platinum-based drugs and how NO can bypass this chemotherapy resistance. Preclinical and clinical studies focused on combination therapy using platinum chemotherapeutic drugs with NO donors have demonstrated antitumor benefits in different types of cancer, particularly non-small cell lung cancer. Altogether, this review aims to summarize the evidence that therapy regimens, including NO donors, are worth considering as new therapeutic options.