Hypoxia, Metabolic Reprogramming, and Drug Resistance in Liver Cancer

Hypoxia, low oxygen (O-2) level, is a hallmark of solid cancers, especially hepatocellular carcinoma (HCC), one of the most common and fatal cancers worldwide. Hypoxia contributes to drug resistance in cancer through various molecular mechanisms. In this review, we particularly focus on the roles of hypoxia-inducible factor (HIF)-mediated metabolic reprogramming in drug resistance in HCC. Combination therapies targeting hypoxia-induced metabolic enzymes to overcome drug resistance will also be summarized. Acquisition of drug resistance is the major cause of unsatisfactory clinical outcomes of existing HCC treatments. Extra efforts to identify novel mechanisms to combat refractory hypoxic HCC are warranted for the development of more effective treatment regimens for HCC patients.

Automated summary

Hypoxia, a hallmark of solid cancers like hepatocellular carcinoma, contributes to drug resistance through molecular mechanisms. This review focuses on HIF-mediated metabolic reprogramming in drug resistance in HCC and suggests combination therapies targeting hypoxia-induced metabolic enzymes to overcome resistance. Efforts to identify novel mechanisms to combat refractory hypoxic HCC are crucial for developing more effective treatment regimens.