Emerging role of NO-mediated therapeutics

Abstract

The free radical nitric oxide (NO) is fundamental in the neoplastic environment. At low concentrations, the gasotransmitter manifests a pathological phenotype characterized by uncontrolled proliferation, increased invasion and metastasis, stimulation of angiogenesis and inhibited apoptosis. Paradoxically, at superphysiological concentrations, a less aggressive phenotype exists, where tumor cells are less likely to metastasize, angiogenesis is inhibited, and apoptotic machinery operates appropriately. This dichotomy of response to NO has created a divergence in the field, with some researchers set on interfering with NO signaling in cancer cells, and others endeavoring to boost it. The purpose of this chapter is to examine the activity of NO in oncology, and to highlight the recent advances in NO-mediated therapeutics. We have focused on emerging strategies that act either by promotion of or interference with NO signaling, including genetic therapies, and have largely limited topics discussed to discoveries from the past 18 months. Attention is paid to agents that have been or are being assessed at clinical trial, and the chapter concludes with a cautionary note on the appropriate use of NO-mediated therapies in oncology.