Nitric oxide donors for prostate and bladder cancers: Current state and challenges

Nitric oxide (NO) is an endogenous molecule that plays pivotal physiological and pathophysiological roles, particularly in cancer biology. Generally, low concentrations of NO (pico- to nanomolar range) lead to tumor promotion. In contrast, high NO concentrations (micromolar range) have pro-apoptotic functions, leading to tumor suppression, and in this case, NO is involved in immune surveillance. Under oxidative stress, inducible NO synthase (iNOS) produces high NO concentrations for antineoplastic activities. Prostate and bladder cancers are the most commonly detected cancers in men, and are related to cancer death in males. This review summarizes the state of the art of NO/NO donors in combating prostate and bladder cancers, highlighting the importance of NO donors in cancer treatment, and the limitations and challenges to be overcome. In addition, the combination of NO donors with classical therapies (radio- or chemotherapy) in the treatment of prostate and bladder cancers is also presented and discussed. The combination of NO donors with conventional anticancer drugs is reported to inhibit tumor growth, since NO is able to sensitize tumor cells, enhancing the efficacy of the traditional drugs. Although important progress has been made, more studies are still necessary to definitely translate the administration of NO donors to clinical sets. The purpose of this review is to inspire new avenues in this topic.