Targeting HIF-2α as therapy for advanced cancers

Drug Discovery Today
Thanabal MurugesanSooriya Kumar

Abstract

Hypoxia-inducible factors (HIF-1α, -2α -3α, and -β) are key factors that control hypoxia-induced carcinogenic pathways. HIF-1α is predominantly involved in the early stages of cancer, whereas HIF-2α is actively involved in the later stages; in addition, chronic (prolonged) rather than acute (short) hypoxia is a feature of metastasis and chemoresistance that occur during the later stages of cancer. Oncometabolites, onco-miRNAs, glucose deprivation, pseudohypoxia, cytokine/chemokine secretion, and some unique upstream proteins are involved in the signaling switch from HIF-1α to HIF-2α; thus, understanding this signaling switch is critical for the treatment of advanced cancer. In this review, we highlight data relating to HIF-2α rather than HIF-1α signaling in cancer pathways and discuss prospective drugs that target this important factor.

Citations

Sep 28, 2018·Journal of Basic and Clinical Physiology and Pharmacology·Thekkuttuparambil A Ajith
Dec 29, 2018·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Deqing LuoHongyue Ren
Oct 3, 2019·Cancer Research·Catherine J LibbyAnita B Hjelmeland
Nov 11, 2019·Trends in Cancer·Daniela MennerichThomas Kietzmann
Oct 29, 2020·Journal of Experimental & Clinical Cancer Research : CR·Tiansheng LiYongguang Tao
Apr 25, 2021·The International Journal of Biochemistry & Cell Biology·Mengchao YuJing Fang

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