Targeting Hypoxia-Inducible Factor-1 (HIF-1) in Cancer: Emerging Therapeutic Strategies and Pathway Regulation

Abstract

Hypoxia-inducible factor-1 (HIF-1) is a key regulator for balancing oxygen in the cells. It is a transcription factor that regulates the expression of target genes involved in oxygen homeostasis in response to hypoxia. Recently, research has demonstrated the multiple roles of HIF-1 in the pathophysiology of various diseases, including cancer. It is a crucial mediator of the hypoxic response and regulator of oxygen metabolism, thus contributing to tumor development and progression. Studies showed that the expression of the HIF-1α subunit is significantly upregulated in cancer cells and promotes tumor survival by multiple mechanisms. In addition, HIF-1 has potential contributing roles in cancer progression, including cell division, survival, proliferation, angiogenesis, and metastasis. Moreover, HIF-1 has a role in regulating cellular metabolic pathways, particularly the anaerobic metabolism of glucose. Given its significant and potential roles in cancer development and progression, it has been an intriguing therapeutic target for cancer research. Several compounds targeting HIF-1-associated processes are now being used to treat different types of cancer. This review outlines emerging therapeutic strategies that target HIF-1 as well as the relevance and regulation of the HIF-1 pathways in cancer. Moreover, it addresses the employment of nanotechnology in developing these promising strategies.

Understanding the Significance of Hypoxia-Inducible Factors (HIFs) in Glioblastoma: A Systematic Review

“…Despite encouraging preclinical results, limited clinical data exist on the efficacy of HIF-related therapies in patients with GBM, necessitating further extensive clinical trials for validation [ 137 , 146 ]. Safety concerns, including potential side effects and toxicity, especially when combined with other treatments, require thorough evaluation [ 147 , 148 , 149 ].…”

Hypoxia-Inducible Factor 1-Alpha (HIF-1α): An Essential Regulator in Cellular Metabolic Control

“…Targeting HIF-1α downstream pathways: The suppression of tumor growth and improvement in treatment outcomes can be achieved by inhibiting HIF-1α-regulated genes involved in angiogenesis (e.g., vascular endothelial growth factor (VEGF) inhibitors) or glycolysis (e.g., glycolytic enzyme inhibitors) [ 32 ].…”