Targeting hypoxia-inducible factor-1alpha: A new strategy for triple-negative breast cancer therapy

Abstract

Triple-negative breast cancer (TNBC) is a subtype of breast cancer that is highly aggressive and hypoxic compared with other subtypes. The role of hypoxia inducible factor 1α (HIF-1α) as a key hypoxic transcription factor in oncogenic processes has been extensively studied. Recently, it has been shown that HIF-1α regulates the complex biological processes of TNBC, such as glycolysis, angiogenesis, invasion and metastasis, breast cancer stem cells (BCSCs) enrichment, and immune escape, to promote TNBC survival and development through the activation of downstream target genes. In addition, inflammatory mediators, oxygen levels, noncoding RNAs, complex signaling regulatory networks, epigenetic regulators are involved in the upstream regulatory expression of HIF-1α. However, further studies are needed to determine the potential and future directions of targeting HIF-1α in TNBC. This article discusses the expression of the HIF-1α transcription factor in TNBC. We also explored the mechanism by which HIF-1α drives TNBC progression. The potential significance of targeting HIF-1α for immunotherapy, chemotherapy, anti-angiogenic therapy, and photodynamic therapy is discussed. The intrinsic mechanism, existing problems and future directions of targeting HIF-1α are also studied.

Keywords: Combination therapy; HIF-1α; Hypoxia; Signaling pathways; TNBC progression; Triple-negative breast cancer.