Hypoxia

Hypoxia, or low oxygen tension, is a universal feature of solid tumors. The tumor microenvironment consists of regions of chronic and acute hypoxia that develop due to the irregular distribution of tumor vessels and limited oxygen diffusion within tumor tissue. While exposure to prolonged or severe hypoxia can be toxic to both normal and cancer cells, cancer cells take particular advantage of their ability to initiate a transcriptional program that allows them to adapt and thrive under these harsh conditions. Importantly, hypoxia upregulates a wide array of signal transduction pathways that drive angiogenesis, cell survival, metabolism, immune evasion, invasion and metastasis. For these reasons, the presence of intratumoral hypoxia is an adverse prognostic factor for patients with solid tumors and is a key component contributing to therapeutic resistance and metastasis. Understanding of the signaling mechanisms and physiological changes that occur in response to hypoxia will lead to alternative and more efficient therapeutic approaches.