Table 1.

The major events led by hypoxia in tumor microenvironment.

Mechanisms	Events
Generation of oxygen free radicals	DNA damage, genomic instability
Proteomic and genomic changes including hypoxia-inducible factor I (HIF1)	Adaptation of the tumor cells to hypoxic condition
Activation of genes that are associated with tumor progression	Metabolic adaptation and cell survival
Upregulation of pro-angiogenic pathways	Stimulation of angiogenesis
Inhibition of apoptosis	Tumor mass increase and treatment resistance
Induction of epithelial–mesenchymal transition in tumor cells	Promotion of invasion and metastasis
Downregulation of adhesion molecules	Tumor cell detachment