Abstract
Tumour hypoxia is significantly correlated with patient survival and treatment outcomes. At the molecular level, hypoxia is a major driving factor for tumour progression and aggressiveness. Despite the accumulative scientific and clinical efforts to target hypoxia, there is still a need to find specific treatments for tumour hypoxia. In this review, we discuss a variety of approaches to alter the low oxygen tumour microenvironment or hypoxia pathways including carbogen breathing, hyperthermia, hypoxia-activated prodrugs, tumour metabolism and hypoxia-inducible factor (HIF) inhibitors. The recent advances in technology and biological understanding reveal the importance of revisiting old therapeutic regimens and repurposing their uses clinically.
Highlights
The presence of low oxygen concentrations, known as hypoxia, is a prevalent characteristic of the microenvironment of solid tumours [1]
Tumour hypoxia causes aggressive tumour progression and treatment resistance, which leads to poor patient survival
Hypoxia arises from an imbalance between oxygen consumption and delivery, which is caused by rapid tumour cell proliferation and an inefficient blood supply carrying oxygen and nutrients [2]
Summary
The presence of low oxygen concentrations, known as hypoxia, is a prevalent characteristic of the microenvironment of solid tumours [1]. Hypoxia arises from an imbalance between oxygen consumption and delivery, which is caused by rapid tumour cell proliferation and an inefficient blood supply carrying oxygen and nutrients [2]. Tumour hypoxia, which is defined as an oxygen tension below 10 mmHg, is significantly correlated with radiation resistance due to the role of oxygen in the ”fixation” of DNA damage. Hypoxia.Briefly, Briefly, carbogen breathing perthermia aim to increase the overall oxygen concentration in tumours, enhancing radiosensitisation; (2) Oxidative phoshyperthermia aim to increase the overall oxygen concentration in tumours, enhancing radiosensitisation; (2) Oxidative phorylation (OXPHOS) inhibitors target mitochondrial metabolism in well-oxygenated cells to promote an increase and phosphorylation (OXPHOS) inhibitors target mitochondrial metabolism in well-oxygenated cells to promote an increase diffusion of the overall oxygen into hypoxic regions and enhance radiation-induced damage; (3) hypoxia-activated proand diffusion of such the overall oxygen into hypoxic regions and radiation-induced damage;. Inhibitors aim to inhibit the hypoxia-induced activation of HIF, selectively targeting hypoxic cells.
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