Chapter 12: Negative Impact of Tumor-Generated Nitric Oxide on Photodynamic Therapy

Many malignant tumors exploit endogenously generated nitric oxide (NO) as a pro-survival molecule, a role often linked to constitutive expression of inducible nitric oxide synthase (iNOS). NO is known to antagonize the antitumor effects of ionizing radiation, chemotherapeutic agents, and also photodynamic therapy (PDT), the latter effect recognized relatively recently. This chapter will focus on low level NO as a tumor-promoting signaling molecule and how it can compromise PDT efficacy by stimulating tumor microvasculature relaxation or more directly by enhancing tumor cell resistance to photokilling and also proliferation, migration, and invasiveness of surviving cells. To be discussed (along with its troubling implications) is the striking observation that for certain cancer cell types, these negative effects are attributable more to PDT stress-induced iNOS/NO than to preexisting iNOS/NO. Approaches for overcoming NO's still poorly recognized anti-PDT activity through pharmacologic use of appropriate iNOS inhibitors will also be discussed.