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

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 ((1)O(2)). With high tumor site-specificity and limited o...

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Detalles Bibliográficos
Autores principales: Girotti, Albert W., Fahey, Jonathan M., Korbelik, Mladen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8143374/
https://www.ncbi.nlm.nih.gov/pubmed/33919266
http://dx.doi.org/10.3390/pharmaceutics13050593
Descripción
Sumario: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 ((1)O(2)). 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.