McKenzie Gordon A G, Hinsley Emma E, Hunter Keith, Lambert Daniel W
College of Medical and Dental Sciences, University of Birmingham, Edgbaston, UK; Unit of Oral and Maxillofacial Pathology, School of Clinical Dentistry, University of Sheffield, Sheffield, UK.
J Oral Pathol Med. 2014 Jul;43(6):395-404. doi: 10.1111/jop.12108. Epub 2013 Aug 20.
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.
头颈部癌症的发病率在全球范围内持续上升，其中主要为鳞状细胞癌（HNSCC）。侵袭性HNSCC预后较差，手术切除带来的不良后遗症促使人们寻找新的治疗干预模式。内皮素（ET）轴由ET-1、ET-2和ET-3组成，它们由内皮素转换酶（ECE）产生，并与ETA受体和ETB受体结合。ET轴在多种人类恶性肿瘤的发生和发展中起作用。已发现ET轴成分在HNSCC中过表达；因此，ET-1拮抗作用和ECE抑制可能是可行的治疗机会。ET-1可通过基质-上皮相互作用促进HNSCC进展，这表明基质也可能是针对ET轴成分的治疗靶点。ET轴还可能提供可作为生物标志物的成分，用于筛查、诊断、监测疾病复发以及对患者进行预后风险分层，同时也可作为局部镇痛的靶点，减少全身副作用。本综述总结了与ET轴相关的当前知识和临床应用潜力。
