The role of HIF-1α in chemo-/radioresistant tumors

Abstract

Chemo-/radioresistance is a major obstacle in clinical oncology. The precise failure mechanisms of chemo-/radioresistance are multifactorial failures. It is now widely accepted that a tumor hypoxia microenvironment contributes significantly to chemo-/radioresistance. Hypoxia is the most common and obvious neoplastic microenvironment and is due to the rapid proliferation of tumor cells. HIF-1α is a principal molecular mediator of adaptability to hypoxia in tumor cells. HIF-1α activation leads to the transcription of a plethora of target genes that promote physiological changes associated with chemo-/radioresistance, including increasing the ability of DNA repair, the inhibition of apoptosis, and alterations of the cellular metabolism. Moreover, recent findings suggest that HIF-1α-activated autophagy is a crucial factor in the promotion of cell survival under the distressed microenvironment, thereby leading to the chemo-/radioresistance. This chapter presents an overview of the role of HIF-1α in chemo-/ radioresistance of tumor cells.