Tumor oxygenation and cancer therapy-then and now.

In 2012, cancer affected 14.1 million people worldwide and was responsible for 8.2 million deaths. The disease predominantly affects aged populations and is one of the leading causes of death in most western countries. In tumors, the aggressive growth of the neoplastic cell population and associated overexpression of pro-angiogenic factors lead to the development of disorganized blood vessel networks that are structurally and functionally different from normal vasculature. A disorganized labyrinth of vessels that are immature, tortuous and hyperpermeable typifies tumor vasculature. Functionally, the ability of the tumor vasculature to deliver nutrients and remove waste products is severely diminished. A critical consequence of the inadequate vascular networks in solid tumors is the development of regions of hypoxia [low oxygen tensions typically defined as oxygen tensions (pO2 values) < 10 mm Hg]. Tumor cells existing in such hypoxic environments have long been known to be resistant to anticancer therapy, display an aggressive phenotype, and promote tumor progression and dissemination. This review discusses the physiological basis of hypoxia, methods of detection, and strategies to overcome the resulting therapy resistance.