Figure 2.

Targeting HIF to overcome hypoxia-associated drug resistance. HIF can be induced by both hypoxia-dependent and -independent mechanisms. Active HIF in tumor cells promotes drug resistance via upregulation of cytoprotective autophagy, receptor tyrosine kinase (RTK) signaling, suppression of apoptosis, and promotion of immunosuppressive tumor microenvironment. Examples of pharmacological approaches targeting HIF-regulating and -regulated mechanisms are shown in red. Small blue arrows indicate the direction of changes of protein abundance or activity after HIF activation.