Hypoxia signaling: Challenges and opportunities for cancer therapy

Mircea Ivan; Melissa L Fishel; Oana M Tudoran; Karen E Pollok; Xue Wu; Paul J Smith

doi:10.1016/j.semcancer.2021.10.002

Hypoxia signaling: Challenges and opportunities for cancer therapy

Semin Cancer Biol. 2022 Oct:85:185-195. doi: 10.1016/j.semcancer.2021.10.002. Epub 2021 Oct 7.

Authors

Mircea Ivan¹, Melissa L Fishel², Oana M Tudoran³, Karen E Pollok⁴, Xue Wu⁵, Paul J Smith⁶

Affiliations

¹ Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA; Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, USA. Electronic address: mivan@iu.edu.
² Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, USA; Department of Pharmacology and Toxicology, IU Simon Comprehensive Cancer Center, Indianapolis, IN, USA.
³ The Oncology Institute "Prof. Dr. Ion Chiricuta", Cluj-Napoca, Cluj, Romania.
⁴ Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, USA.
⁵ Ohio State University, Columbus, OH, USA.
⁶ School of Medicine, Cardiff University, Cardiff, UK.

Abstract

Hypoxia is arguably the first recognized cancer microenvironment hallmark and affects virtually all cellular populations present in tumors. During the past decades the complex adaptive cellular responses to oxygen deprivation have been largely elucidated, raising hope for new anti cancer agents. Despite undeniable preclinical progress, therapeutic targeting of tumor hypoxia is yet to transition from bench to bedside. This review focuses on new pharmacological agents that exploit tumor hypoxia or interfere with hypoxia signaling and discusses strategies to maximize their therapeutic impact.

Keywords: HIF inhibitors; HIF1; HIF2; Hypoxia; Hypoxia-activated prodrug.

Publication types

Review
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Basic Helix-Loop-Helix Transcription Factors* / metabolism
Cell Hypoxia
Humans
Hypoxia
Neoplasms* / drug therapy
Neoplasms* / etiology
Signal Transduction
Tumor Microenvironment

Substances

Basic Helix-Loop-Helix Transcription Factors

Abstract

Publication types

MeSH terms

Substances

Grants and funding