The role of HIF in cancer
Hypoxia is a common feature of all solid tumors and their metastases.
Hypoxia-inducible factor 1-alpha (HIF-1α) and HIF-2α are master transcriptional regulators of the hypoxia response, whereas the role of HIF-3α, with its multiple isoforms, has not been clearly defined.
The most fundamental response to hypoxia involves hypoxia-inducible factor (HIF)-driven transcriptional changes that promote survival during hypoxic stress. These ‘HIF axes’ include the induction of angiogenesis, metabolic reprogramming, and immune modulation, which together play a central role in driving tumor progression and morbidity.
The HIF axes are validated targets for cancer therapy but are plagued by the acquisition of resistance due to the activation of alternative, bypass mechanisms.
The challenges ahead lie in the identification of novel, non-redundant targets and unique treatment combinations that can circumvent resistance mechanisms.
https://www.cell.com/trends/biochemical-sciences/fulltext/S0968-0004(25)00135-5
