Gasotransmitters in cancer: from pathophysiology to experimental therapy

The gasotransmitters nitric oxide, carbon monoxide and hydrogen sulfide are involved in a large number of physiological processes. In this Review, the author explains how, in cancer, each of these gaseous mediators exhibits a biphasic pharmacological character, whereby increasing or decreasing gasotransmitter concentrations in the tumour can exert antitumour effects. The three endogenous gaseous transmitters — nitric oxide (NO), carbon monoxide (CO) and hydrogen sulfide (H2S) — regulate a number of key biological functions. Emerging data have revealed several new mechanisms for each of these three gasotransmitters in tumour biology. It is now appreciated that they show bimodal pharmacological character in cancer, in that not only the inhibition of their biosynthesis but also elevation of their concentration beyond a certain threshold can exert anticancer effects. This Review discusses the role of each gasotransmitter in cancer and the effects of pharmacological agents — some of which are in early-stage clinical studies — that modulate the levels of each gasotransmitter. A clearer understanding of the pharmacological character of these three gases and the mechanisms underlying their biological effects is expected to guide further clinical translation.