Acuña-Pilarte Karen, Koh Mei Yee
Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, UT 84112, USA.
Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, UT 84112, USA.
Trends Biochem Sci. 2025 Aug;50(8):677-694. doi: 10.1016/j.tibs.2025.06.005. Epub 2025 Jul 9.
The hypoxia-inducible factors (HIFs) are central transcriptional mediators of the cellular response to hypoxia. HIF activation typically drives a physiologically beneficial adaptive response to hypoxia. However, within solid tumors, the HIF-driven adaptation to hypoxia results in alterations within major cancer cell signaling axes, including those regulating angiogenesis, metabolism, and immune modulation, which profoundly impact tumor progression. This review describes established and recent findings of the role of HIFs in the regulation of these major axes, and the impact of the 'HIF axes' on tumor progression and response to therapy. Current and emerging therapies targeting these axes will also be discussed.
缺氧诱导因子（HIFs）是细胞对缺氧反应的核心转录调节因子。HIF激活通常会驱动对缺氧的生理有益适应性反应。然而，在实体瘤中，HIF驱动的对缺氧的适应性会导致主要癌细胞信号轴发生改变，包括那些调节血管生成、代谢和免疫调节的信号轴，这对肿瘤进展产生深远影响。本综述描述了HIFs在调节这些主要信号轴中的作用的既定和最新发现，以及“HIF信号轴”对肿瘤进展和治疗反应的影响。还将讨论针对这些信号轴的现有和新兴疗法。
