The occurrence of hypoxia is common in many solid tumors, and it enhances aggressive features of cancer such as cell survival, angiogenesis, and metastasis while minimizing the efficacies of chemotherapy and radiotherapy. Hypoxia also plays a pivotal role in regulating immune cell function which is important for immunotherapy. Hypoxia-inducible factor has been suggested as a master regulator of tumor cell adaptation to the hypoxic microenvironment. Currently, several approaches have been proposed to eliminate the hypoxic state in tumors for delaying cancer progression and improving therapeutic efficacy. In this review, we summarize current findings on the relevance of hyperoxia-based therapeutics for cancer treatment. Accumulating evidence indicates that hyperoxic therapy inhibits tumor growth and increases treatment efficacy. Primary antitumor effect of hyperoxic therapy may be due to the reversal of tumor hypoxia and the generation of reactive oxygen species. Restoring immune function is also suggested as a potential mechanism. Hyperoxic therapy can also cause cellular injury and organ dysfunction. In conclusion, overcoming tumor hypoxia is a major problem that needs to be solved. Further studies to standardize and personalize hyperoxia therapy according to the type of cancer, stage, and comorbidities are needed.
Impact statement
Tumor hypoxia promotes cancer cell aggressiveness, and is strongly associated with poor prognosis across multiple tumor types. The hypoxic microenvironments inside tumors also limit the effectiveness of radiotherapy, chemotherapy, and immunotherapy. Several approaches to eliminate hypoxic state in tumors have been proposed to delay cancer progression and improve therapeutic efficacies. This review will summarize current knowledge on hyperoxia, used alone or in combination with other therapeutic modalities, in cancer treatment. Molecular mechanisms and undesired side effects of hyperoxia will also be discussed.
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