Hypoxia and Predicting Radiation Response

The results from many studies indicate that most solid tumors, regardless of site of origin, contain hypoxic regions. Experimental studies have demonstrated that, apart from the well-known protective effect of hypoxia on the radiation response of cells and tissues, hypoxic conditions can also result in modified gene expression patterns, causing (to a greater or lesser extent in different cell populations) genomic instability, increased invasive capacity, higher propensity to metastasize, enhanced stem cell properties, and ability to survive nutrient deprivation. Clinical trials of hypoxia-targeted treatments have demonstrated improved local tumor control and patient survival in a number of tumor sites. However, our improved understanding of the underlying biology of cellular responses to hypoxia, and its potential interactions with the heterogeneous nature of tumor phenotypes, makes it likely that not every tumor that contains regions of hypoxia would necessarily need (or benefit from) such treatments. New more effective treatments are emerging, but it is likely that these treatments would have the biggest clinical effect in situations where tumor hypoxia is a primary driver of cancer behavior. The challenge for the Radiation Oncology community is the development of robust precision cancer medicine strategies for identifying patients with such tumors, in the setting of other etiological, genomic, and host-tumor factors, and treating these patients with the appropriate hypoxia-targeting strategy to reduce the effect of hypoxia on radiation treatment response. In this context, it is important to consider not only the hypoxic state of the tumor at diagnosis but also the changing characteristics of this state during the course of treatment.