Inhibition of the HIF-1 Survival Pathway as a Strategy to Augment Photodynamic Therapy Efficacy

on behalf of the Photodynamic Therapy Study Group

Research output: Chapter in Book/Report/Conference proceedingChapterAcademicpeer-review

Abstract

Photodynamic therapy (PDT) is a non-to-minimally invasive treatment modality that utilizes photoactivatable drugs called photosensitizers to disrupt tumors with locally photoproduced reactive oxygen species (ROS). Photosensitizer activation by light results in hyperoxidative stress and subsequent tumor cell death, vascular shutdown and hypoxia, and an antitumor immune response. However, sublethally afflicted tumor cells initiate several survival mechanisms that account for decreased PDT efficacy. The hypoxia inducible factor 1 (HIF-1) pathway is one of the most effective cell survival pathways that contributes to cell recovery from PDT-induced damage. Several hundred target genes of the HIF-1 heterodimeric complex collectively mediate processes that are involved in tumor cell survival directly and indirectly (e.g., vascularization, glucose metabolism, proliferation, and metastasis). The broad spectrum of biological ramifications culminating from the activation of HIF-1 target genes reflects the importance of HIF-1 in the context of therapeutic recalcitrance. This chapter elaborates on the involvement of HIF-1 in cancer biology, the hypoxic response mechanisms, and the role of HIF-1 in PDT. An overview of inhibitors that either directly or indirectly impede HIF-1-mediated survival signaling is provided. The inhibitors may be used as pharmacological adjuvants in combination with PDT to augment therapeutic efficacy.

Original languageEnglish
Title of host publicationPhotodynamic Therapy
Subtitle of host publicationMethods and Protocols
EditorsMans Broekgaarden, Hong Zhang, Mladen Korbelik, Michael R. Hamblin, Michal Heger
PublisherHumana Press
Chapter19
Pages285-403
Number of pages119
Edition1
ISBN (Electronic)978-1-0716-2099-1
ISBN (Print)978-1-0716-2098-4, 978-1-0716-2101-1
DOIs
Publication statusPublished - 4 May 2022

Publication series

NameMethods in Molecular Biology
PublisherHumana
Volume2451
ISSN (Print)1064-3745
ISSN (Electronic)1940-6029

Keywords

  • Hypoxia-inducible factor 1
  • Pharmacology, Inhibitor
  • Photobiology and photochemistry
  • Survival signaling
  • Tumor biology and biochemistry

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