Investigating hypoxia-inducible factor signaling in cancer: Mechanisms, clinical implications, targeted therapeutic strategies, and resistance

Highlights

•Hypoxia-inducible factors (HIFs) regulate genes involved in angiogenesis, invasion and metabolic reprogramming, essential for cancer progression.

•HIF-1α triggers metabolic changes, including the Warburg effect, to promote tumor survival.

•HIF signaling enhances resistance to chemotherapy and radiation via drug efflux pumps and accelerates DNA repair.

•Natural and synthetic HIF inhibitors, including BAY 87–2243 and glyceollin, are being studied for cancer treatment.

The combination of HIF inhibitors and conventional therapies demonstrates potential for enhancing cancer treatment results.