Effect of epigenetic changes in hypoxia induced factor (HIF) gene across cancer types

Abstract

Cancer hypoxia, a crucial characteristic of malignancy, ranging from practically non-hypoxic to severe, impacts gene expression, metabolism and mechanisms associated with tumor formation serves as a key obstacle in cancer therapy. It triggers a complex network of cell signaling pathways, such as the NF-κB, PI3K, mTOR/AKT, MAPK, HIF and their associated genes regulating the effects of the same. The onset and advancement of cancer are attributed to genetic and epigenetic modifications which are intrinsically related. Off late, it has been observed that in disease progression, the epigenetic modifications lead to gene mutations that in turn alter the epigenome, presenting a major hurdle in fabricating treatment strategies. However, the progress in science and technology has led to the emergence of various surfacing omics and multi-view clustering algorithms, which offer unparalleled prospects for further subtyping cancers, enhancing the prognosis and treatment results of these subtypes, and comprehending crucial pathophysiological mechanisms across diverse molecular strata. Multi-omics has allowed scientists to gain a more comprehensive understanding of the various ways that cellular malfunction can lead to cancer. So, it becomes of utmost importance to firstly understand the epigenetic changes taking place in tumor hypoxia at gene level. This review sheds light on the role of HIF gene in hypoxic milieu and its relationship with mechanisms of cancer epigenetics. It further glances as to how omics approach can be used to study the oncogenic cellular changes and how bioinformatic tools aid in identification of complex gene networks involved in disease progression. Lastly, it glimpses through the benefits and shortcomings of the existing epi drug therapy and how it can be used in developing novel treatment options.