Tumor hypoxia

Condition of low oxygen in tumor tissues

Tumor hypoxia refers to a condition in which there is a deficiency of oxygen in the tumor microenvironment. This phenomenon is a common characteristic of solid tumors and has significant implications for cancer progression and treatment.

Pathophysiology

Tumor hypoxia occurs when the rapid growth of cancer cells outpaces the development of new blood vessels, leading to areas within the tumor that are poorly oxygenated. This hypoxic environment can influence tumor biology in several ways, including promoting angiogenesis, altering metabolism, and affecting cell signaling pathways.

Hypoxia-Inducible Factors

The primary cellular response to hypoxia is mediated by hypoxia-inducible factors (HIFs), which are transcription factors that regulate the expression of genes involved in adaptation to low oxygen conditions. HIF-1, in particular, plays a crucial role in the regulation of genes that control glycolysis, angiogenesis, and cell survival.

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Diagram showing the interaction between tumor stroma and extracellular matrix in hypoxia.

Metabolic Adaptations

Under hypoxic conditions, cancer cells often switch from oxidative phosphorylation to anaerobic glycolysis to meet their energy demands. This metabolic shift is known as the Warburg effect.

Glycolytic Pathway

HIF-1 upregulates the expression of several glycolytic enzymes, including GLUT1 (glucose transporter 1), which facilitates increased glucose uptake, and 6-phosphofructo-2-kinase, which enhances glycolytic flux.

GLUT1 transporter facilitates glucose uptake in hypoxic conditions.

Lactate Production

The end product of anaerobic glycolysis is lactic acid, which accumulates in the tumor microenvironment, contributing to acidosis and further promoting tumor progression.

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3D structure of lactic acid.

Impact on Treatment

Tumor hypoxia is associated with resistance to radiotherapy and certain chemotherapy agents. This resistance arises because oxygen is a potent radiosensitizer, and its absence reduces the effectiveness of radiation-induced DNA damage.

Research and Therapeutic Strategies

Efforts to overcome hypoxia-induced treatment resistance include the development of hypoxia-activated prodrugs and the use of agents that can modify the tumor microenvironment to improve oxygenation.

Related pages

• Angiogenesis
• Cancer metabolism
• Hypoxia-inducible factor

References

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