Insights Into the Crosstalk of HIF and Autophagy: Regulation Mechanisms and Therapeutic Potentials in Cancer

Hypoxic and nutrient-deprived conditions are characteristics of the solid tumors' microenvironment (TME), where hypoxia-inducible factor (HIF) and autophagy serve as the central modulators in cancer cells. Herein, we synthesize decades of research regarding HIF and autophagy in cancer, highlighting their regulatory roles in modulating progression, such as HIF-1α-BNIP3/BNIP3L-Beclin-1 complex signaling and HIF-mTOR-ULK1 axis. Given the paucity of comprehensive syntheses regarding this intricate interplay, we systematically deconstruct recent findings to map the molecular landscape connecting HIF-1 to autophagic flux and cell death. Specifically, we explore the metabolic bridges linking HIF and autophagy, including glycolysis and reactive oxygen species (ROS). Furthermore, by refining the content of dual-target molecules, we propose strategies for co-targeting HIF and autophagy, aiming to catalyze the development of novel therapeutic interventions.