Hypoxia-mediated cancer stem cell resistance and targeted therapy

Highlights

• Cancer stem cells (CSCs) are regarded as one of the important targets that mediate tumor resistance.

• Tumor hypoxic microenvironment plays an important role in regulating resistance of CSCs to chemotherapy and radiotherapy.

• Hypoxia maintains the stemness of CSCs through regulation of self-renewal signaling pathways, microRNAs, drug transporters and EMT.

• HIFs have emerged as therapeutic targets in cancer therapy.

Abstract

Drug resistance is a major obstacle in the treatment of tumors, which easily lead to relapse or poor prognosis. Cancer stem cells (CSCs) are regarded as one of the important targets that mediate tumor resistance. Increasing evidence shows that the tumor hypoxia microenvironment is closely related to the resistance of CSCs to chemotherapy and radiotherapy. In this review, we intend to review the articles that have described how the hypoxic microenvironment affects CSC stemness and mediates tumor resistance and provide new directions and methods in the clinical treatment of tumors. Here, we also discuss the feasibility and development prospects of using hypoxia-inducible factors (HIFs) that regulate the hypoxic microenvironment of tumors as targeted agents to treat tumors, as well as to reduce or even reverse the resistance of tumors to chemotherapy and radiotherapy.