Time, location and function of hypoxia-inducible factors are critical to therapeutic tumour response

Abstract

Multiple lines of evidence confirm isoforms the strong association between the presence of hypoxia in solid tumours and poorer outcomes ihn patients with cancer resulting from both more aggressive tumour cell behaviour and impaired responses to therapy.1 2 With well over 12 000 articles published in the past 5 years alone (source, PubMed), the importance of hypoxia in cancer is indisputable. The impact of hypoxia on cancer cell biology takes multiple forms, but the regulation of the hypoxia-inducible factor (HIF), sits at its core. The review written by Ortmann3 provides an extensive overview of the regulation, function and therapeutic potential of these key dimeric protein complexes. The clarification that several isoforms of HIF exist, classified as 1, 2 or 3, and the fact that they operate in a chromatin environment that is also influenced by oxygenation immediately highlights te complexity in the molecular adaptation of cells, including cancer cells, to modifications in oxygen availability.