Photodynamic Therapy as an Oxidative Anti-Tumor Modality: Negative Effects of Nitric Oxide on Treatment Efficacy.

Pharmaceutics

Department of Integrative Oncology, BC Cancer, Vancouver, BC V5Z 1L3, Canada.

Published: April 2021

Anti-tumor photodynamic therapy (PDT) is a unique oxidative stress-based modality that has proven highly effective on a variety of solid malignancies. PDT is minimally invasive and generates cytotoxic oxidants such as singlet molecular oxygen (O). With high tumor site-specificity and limited off-target negative effects, PDT is increasingly seen as an attractive alternative or follow-up to radiotherapy or chemotherapy. Nitric oxide (NO) is a short-lived bioactive free radical molecule that is exploited by many malignant tumors to promote cell survival, proliferation, and metastatic expansion. Typically generated endogenously by inducible nitric oxide synthase (iNOS/NOS2), low level NO can also antagonize many therapeutic interventions, including PDT. In addition to elevating resistance, iNOS-derived NO can stimulate growth and migratory aggressiveness of tumor cells that survive a PDT challenge. Moreover, NO from PDT-targeted cells in any given population is known to promote such aggressiveness in non-targeted counterparts (bystanders). Each of these negative responses to PDT and their possible underlying mechanisms will be discussed in this chapter. Promising pharmacologic approaches for mitigating these NO-mediated responses will also be discussed.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8143374PMC
http://dx.doi.org/10.3390/pharmaceutics13050593DOI Listing

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