Tumor hypoxia presents a unique therapeutic challenge in the treatment of solid
malignancies. Not only does the presence of
hypoxia compromise the efficacy of locally-directed
therapies, such as
radiotherapy, but the proteomic and genomic changes activated by
hypoxia can promote malignant progression and systemic dissemination. In an effort to improve therapeutic ratios and treatment outcomes,
therapies that specifically target areas of
hypoxia are actively being investigated. Therefore, functional noninvasive methods of assessing tumor hypoxia, such as imaging via positron emission tomography/computed tomography, are warranted. Multiple imaging agents are currently being used or investigated to evaluate
hypoxia status before
therapy and to measure changes in oxygenation during treatment, as a means to optimizing therapeutic regimens. Advances in therapeutic radiation delivery, such as intensity-modulated
radiation therapy, and
proton therapy now allow for differential targeting of
tumor areas, with potential dose escalation via dose painting to areas of greatest treatment resistance. The incorporation of novel imaging markers into the
multimodal treatment paradigm, whether with radiation dose escalation or in concert with agents that reverse tumor hypoxia, hypoxic radiosensitizers, or hypoxic
cytotoxins, will be a vital component of advancing clinical individualized
cancer care and improving cure rates.