Evaluation of the Impact of Nitric Oxide on Resistance to Platinum-Based Chemotherapeutics.

Ahlam Ali, Cian McCrudden, Helen McCarthy

Research output: Chapter in Book/Report/Conference proceedingChapter (peer-reviewed)

Abstract

One of the most persistent problems in the treatment and management of cancer is the development of resistance to therapy in the cancerous cells. The mechanisms of resistance can be intrinsic or can be acquired through exposure to chemotherapeutic agents. Accumulating clinical experience, supported by data from animal models, indicates that chemotherapy is most effective when given in combination to achieve additive or synergistic effects that reduce the potential development of drug resistance.

Platinum compounds are one of the most widely used classes of agents in cancer therapy; however, platinum drugs approved for clinical use are rarely given to patients as a monotherapy. A concept that is emerging is the utilization of a biological messenger to abrogate the development of resistance. One such agent is the gasotransmitter nitric oxide (NO), which has recently been implicated in several mechanisms of cytotoxicity by platinum agents. Release of NO can potentiate the cytotoxic effects of platinum chemotherapeutics, either by direct synergistic cytotoxic effects or by increase of blood supply and vascular permeability, thus increasing tumor perfusion and consequently the amount of chemotherapy reaching the tumor. Combined understanding of how platinum drugs work, and the mechanisms by which NO can abrogate resistance should allow for the development of new combination regimens. This chapter discusses the clinical importance of cisplatin and related platinum-based drugs for the treatment of various human cancers, highlighting the potential use of NO as a chemosensitizer. Special attention is paid to the molecular mechanisms underlying resistance, and the role of NO to reverse chemoresistance of tumor cells.
Original languageEnglish
Title of host publicationNitric Oxide (Donor/Induced) in Chemosensitizing
PublisherElsevier
ChapterChapter 5
Pages71-90
Number of pages19
Publication statusPublished - 22 Sep 2017

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