子宫肌瘤是女性最常见的肿瘤，影响全球多达 70% 的女性，但有针对性的治疗选择有限。氧化应激最近已成为子宫肌瘤发病机制的关键驱动因素，并为缺氧诱导的细胞转化、细胞外基质病理生理学、缺氧细胞信号级联和子宫生物学提供了见解。缺氧通过以下方式驱动肌瘤肿瘤发生：(1) 促进子宫肌层干细胞增殖，(2) 引起 DNA 损伤，推动干细胞向肿瘤起始细胞转化，以及 (3) 导致细胞外基质 (ECM) 产生过多。常见的肌瘤相关 DNA 突变包括 MED12 突变、HMGA2 过度表达和富马酸水合酶功能丧失。有证据表明缺氧信号传导与这些突变之间存在相互作用。缺氧触发的细胞信号传导通过各种途径（包括 HIF-1、TGFβ 和 Wnt/β-连环蛋白）促进肌瘤的发育和生长。由于抗氧化失衡、ECM 积累和生长超出了足够的血管供应，肌瘤相关的缺氧持续存在。目前临床上可用的肌瘤治疗方法并未利用缺氧靶向疗法。越来越多的临床前和临床研究发现，ROS 抑制剂、抗 HIF-1 药物、Wnt/β-连环蛋白抑制和 TGFβ 级联抑制剂可以通过靶向缺氧来减少肌瘤的发育和生长。

Uterine fibroids are the most common tumors in females affecting up to 70% of women world-wide, yet targeted therapeutic options are limited. Oxidative stress has recently surfaced as a key driver of fibroid pathogenesis and provides insights into hypoxia-induced cell transformation, extracellular matrix pathophysiology, hypoxic cell signaling cascades, and uterine biology. Hypoxia drives fibroid tumorigenesis through (1) promoting myometrial stem cell proliferation, (2) causing DNA damage propelling transformation of stem cells to tumor initiating cells, and (3) driving excess extracellular matrix (ECM) production. Common fibroid-associated DNA mutations include MED12 mutations, HMGA2 overexpression, and Fumarate hydratase loss of function. Evidence suggests an interaction between hypoxia signaling and these mutations. Fibroid development and growth are promoted by hypoxia-triggered cell signaling via various pathways including HIF-1, TGFβ, and Wnt/β-catenin. Fibroid-associated hypoxia persists due to antioxidant imbalance, ECM accumulation, and growth beyond adequate vascular supply. Current clinically available fibroid treatments do not take advantage of hypoxia-targeting therapies. Growing pre-clinical and clinical studies identify ROS inhibitors, anti-HIF-1 agents, Wnt/β-catenin inhibition, and TGFβ cascade inhibitors as agents that may reduce fibroid development and growth through targeting hypoxia.