How to deal with the relationship between hypoxia and radiotherapy in the hypofractionated radiotherapy era?

Hypoxia, a common phenomenon in solid tumors can promote dysfunctional vascular growth and epithelial-to-mesenchymal transition, leading to cell mobility and metastasis. the decreased sensitivity of hypoxic tumor cells to ionizing radiation is one of the main factors affecting the effect of conventional radiotherapy. it is well known that conventional radiotherapy mainly reduces the effect of hypoxic radiation resistance by reoxygenation between fractions. with the improvement of radiation treatment planning and delivery, more and more cancer patients have been treated with hypofractionated radiotherapy (hfrt), which have achieved a much higher effect than conventional radiotherapy. given that hfrt is delivered within one or a few fractions, does tumor hypoxia affect its efficacy? is there any way to further improve the effect of hfrt? in this review, we focus on the interaction between hfrt and hypoxia, and how to optimize the regimen of hfrt to decrease the effect of hypoxia and improve the efficacy is discussed in detail.