The incidence of head and neck cancer, predominantly consisting of squamous cell carcinomas (HNSCCs), is continuing to rise worldwide. Invasive HNSCC carries a poor prognosis, and the detrimental sequelae of surgical resection motivate identification of novel modes of therapeutic intervention. The endothelin (ET) axis consists of ET-1, 2 and 3, which are generated by endothelin-converting enzyme (ECE) and engage with the receptors ETA R and ETB R. The ET axis plays a role in the development and progression of various human malignancies. ET axis components have been found to be overexpressed in HNSCC; ET-1 antagonism and inhibition of ECE may therefore represent viable therapeutic opportunities. ET-1 can promote HNSCC progression via stromal-epithelial interactions, suggesting that the stroma may also hold potential for therapies targeting components of the ET axis. The ET axis may also offer components that can be used as biomarkers - for screening, diagnosis, monitoring disease recurrence and prognostic risk stratification of patients - and targets for localised analgesia offering less systemic side effects. This review summarises the current knowledge and potential for clinical opportunities related to the ET axis.

译文

:头颈癌的发病率主要由鳞状细胞癌(HNSCC)组成,在世界范围内仍在继续上升。浸润性HNSCC预后较差,手术切除的后遗症促使人们识别新型的治疗干预方式。内皮素(ET)轴由ET-1、2和3组成,它们由内皮素转化酶(ECE)生成并与受体ETA R和ETB R结合。各种人类恶性肿瘤。已经发现ET轴组件在HNSCC中过表达;因此,ET-1拮抗作用和对ECE的抑制可能代表了可行的治疗机会。 ET-1可以通过基质-上皮相互作用促进HNSCC进程,表明基质可能还具有靶向ET轴成分的治疗潜能。 ET轴还可提供可用作生物标志物的成分-用于筛查,诊断,监测疾病复发和患者的预后风险分层-以及用于局部镇痛的靶标,其系统副作用较小。这篇综述总结了与ET轴相关的当前知识和潜在的临床机会。

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