Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer, with increasing incidence worldwide. In this survey, we evaluate different aspects of hypoxia and its effect on the course of HCC.

by searching PUBMED and Scopus DATA base from 2012 to 2017.

Hypoxia (Oxygen O2 deprivation) is frequently found in regions of HCC due to abnormal tumor vasculature. HCC shares the character of tissue hypoxia with other solid tumors, especially when the tumor grows quickly and angiogenesis fails to catch up with the speed of tumor growth. Hypoxia can promote tumor progression and induce radiation and chemotherapy resistance. Hypoxia-inducible factor (HIF-1) is an important transcription factor involved in the hypoxic response of cells and their functions in tumor development and progression. Among the subunits of HIF-1, HIF-1α has been implicated in cancer progression. Expression of HIF is closely associated with metastasis and poor prognosis in HCC. HIF is the central regulator of HCC metastasis, HIF inhibitors are attractive tools when used alone or as combined treatment to curb HCC metastasis. HIF-1α should therefore be a promising molecular target for the development of anti-HCC agents. High expression of HIF-1α and its regulatory effect on angiogenesis-related factors are closely associated with patients′ tolerance to radiotherapy and chemoradiotherapy, tumor invasion, metastasis, and prognosis. Hypoxia-inducible factor (HIF)-2α is regarded as a preferential target for individualized HCC treatment and sorafenib resistance. Sorafenib inhibits HIF-1α synthesis, making the hypoxic response to be switched from HIF-1α- to HIF-2α-dependent pathways and providing a mechanism for more aggressive growth of HCC.

Hypoxia promotes HCC progression and therapy resistance, and there is not any systemic treatment for HCC patients after sorafenib resistance.