Targeting cyclic hypoxia to prevent malignant progression and therapeutic resistance of cancers.

Emerging evidence shows that cyclic hypoxia exists in most solid cancers. It is believed that under cyclic hypoxic conditions cancer cells exhibit more malignant biological behaviors than under chronic hypoxic conditions. In this review, we provide a collection of evidence showing the molecular mechanisms by which cyclic hypoxia induces aggressiveness, malignant progression, and therapeutic resistance in cancers. Moreover, we propose that cyclic hypoxia is responsible for the regulation of cancer stem cells, which possess typical biological characteristics of therapeutic resistance. Based on the present findings, some key factors regulated by cyclic hypoxia may serve as potential targets for the prevention of malignant progression and the treatment of solid cancers. Much research is necessary to gain further insights into the biological aspects of cyclic hypoxia in the development and progression of cancers.