Endometriosis (EM) is defined as endometrial tissues found outside the uterus. Growth and development of endometriotic cells in ectopic sites can be promoted via multiple pathways, including MAPK/MEK/ERK, PI3K/Akt/mTOR, NF-κB, Rho/ROCK, reactive oxidative stress, tumor necrosis factor, transforming growth factor-β, Wnt/β-catenin, vascular endothelial growth factor, estrogen, and cytokines. The underlying pathophysiological mechanisms include proliferation, apoptosis, autophagy, migration, invasion, fibrosis, angiogenesis, oxidative stress, inflammation, and immune escape. Current medical treatments for EM are mainly hormonal and symptomatic, and thus the development of new, effective, and safe pharmaceuticals targeting specific molecular and signaling pathways is needed. Here, we systematically reviewed the literature focused on pharmaceuticals that specifically target the molecular and signaling pathways involved in the pathophysiology of EM. Potential drug targets, their upstream and downstream molecules with key aberrant signaling, and the regulatory mechanisms promoting the growth and development of endometriotic cells and tissues were discussed. Hormonal pharmaceuticals, including melatonin, exerts proapoptotic via regulating matrix metallopeptidase activity while nonhormonal pharmaceutical sorafenib exerts antiproliferative effect via MAPK/ERK pathway and antiangiogenesis activity via VEGF/VEGFR pathway. N-acetyl cysteine, curcumin, and ginsenoside exert antioxidant and anti-inflammatory effects via radical scavenging activity. Natural products have high efficacy with minimal side effects; for example, resveratrol and epigallocatechin gallate have multiple targets and provide synergistic efficacy to resolve the complexity of the pathophysiology of EM, showing promising efficacy in treating EM. Although new medical treatments are currently being developed, more detailed pharmacological studies and large sample size clinical trials are needed to confirm the efficacy and safety of these treatments in the near future.

中文翻译：

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针对子宫内膜异位症信号通路的药物作为潜在的新疗法：综述

子宫内膜异位症（EM）被定义为在子宫外发现的子宫内膜组织。多种途径可促进异位子宫内膜异位细胞的生长发育，包括MAPK/MEK/ERK、PI3K/Akt/mTOR、NF-κB、Rho/ROCK、反应性氧化应激、肿瘤坏死因子、转化生长因子-β 、Wnt/β-连环蛋白、血管内皮生长因子、雌激素和细胞因子。潜在的病理生理机制包括增殖、凋亡、自噬、迁移、侵袭、纤维化、血管生成、氧化应激、炎症和免疫逃逸。目前针对 EM 的药物治疗主要是激素治疗和对症治疗，因此需要开发针对特定分子和信号通路的新型、有效和安全的药物。在这里，我们系统地回顾了专门针对 EM 病理生理学分子和信号通路的药物的文献。讨论了潜在的药物靶点、具有关键异常信号传导的上下游分子，以及促进子宫内膜异位细胞和组织生长和发育的调控机制。激素药物（包括褪黑激素）通过调节基质金属肽酶活性发挥促凋亡作用，非激素药物索拉非尼通过 MAPK/ERK 途径发挥抗增殖作用，通过 VEGF/VEGFR 途径发挥抗血管生成活性。N-乙酰半胱氨酸、姜黄素和人参皂苷通过自由基清除活性发挥抗氧化和抗炎作用。天然产品功效高、副作用小；例如，白藜芦醇和表没食子儿茶素没食子酸酯具有多个靶点并具有协同功效，可以解决EM病理生理学的复杂性，在治疗EM方面显示出良好的疗效。尽管目前正在开发新的药物治疗方法，但在不久的将来还需要更详细的药理学研究和大样本临床试验来证实这些治疗方法的有效性和安全性。