Figure 2.

A hypothetic model illustrates that malignant progression results from antiangiogenic therapy. Angiogenic inhibition deprives tumor cells of oxygen and nutrients, resulting in vessel regression and thereby death of the majority of the tumor cells. However, hypoxic cells harbored within the solid tumor are able to tolerate severe hypoxia by undergoing genetic alterations for malignant progression via the HIF-1α–c-Myc pathway and by inducing angiogenesis and glycolysis for cell proliferation via the HIF-1α–ARNT pathway.

Abbreviations: HIF, hypoxia-inducible factor; ARNT, aryl hydrocarbon receptor nuclear translocator.