Can Nitric Oxide-Based Therapy Be Improved for the Treatment of Cancers? A Perspective

Since the early observations that nitric oxide ((•)NO) at high concentrations is cytotoxic to cancer cells and that it may play an important role in the treatment of human cancers, a significant number of compounds (NO-donors) have been prepared to deliver (•)NO to tumors. (•)NO also sensitizes various clinically active anticancer drugs and has been shown to induce the reversal of multi-drug resistance in tumor cells expressing ATP-binding cassette-transporter proteins. For the successful treatment of cancers, (•)NO needs to be delivered precisely to tumors, and its adverse toxicity must be limited. Like other chemotherapeutics, the precise delivery of drugs has been a problem and various attempts have been made, such as the encapsulation of drugs in lipid polymers, to overcome this. This prospective study examines the use of various strategies for delivering (•)NO (using NO-donors) for the treatment of cancers. Finding and utilizing such a delivery system is an important step in delivering cytotoxic concentrations of (•)NO to tumors without adverse reactions, leading to a successful clinical outcome for patient management.