Targeting the transforming growth factor-β signalling pathway in metastatic cancer
Targeting the transforming growth factor-β signalling pathway in metastatic cancer
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DOI：
10.1016/j.ejca.2010.02.040
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发表时间：
2010-05-01
影响因子：
8.4
通讯作者：
Kang, Yibin
中科院分区：
文献类型：
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作者：
Korpal, Manav;Kang, Yibin
转化生长因子 (TGF)-β 信号传导在肿瘤进展中发挥着双重作用，在早期充当肿瘤抑制因子，在晚期充当促转移途径。越来越多的证据表明，晚期肿瘤会产生过量的 TGF-β，从而促进肿瘤生长、侵袭和次要器官定植。鉴于促转移功能，目前正在探索许多策略来拮抗 TGF-β 途径作为转移性癌症的治疗方法。使用大分子配体陷阱、使用反义技术降低 TGF-β 配体的翻译效率以及使用小分子抑制剂拮抗 TGF-β 受体 I/II 激酶功能等策略是当今正在探索的最重要的方法。单独使用抗 TGF-β 疗法或与免疫抑制或细胞毒性疗法联合使用，在临床前和临床环境中已取得了有希望的结果。尽管取得了这些成功，但 TGF-β 信号传导在癌症中的时间和环境依赖性作用使得定义最有可能产生反应的患者亚组以及在临床中最有效的治疗方案变得具有挑战性。目前正在开发新型小鼠模型和诊断工具来规避这些问题，这可能会加速抗 TGF-β 药物的开发和临床应用。 (C) 2010 Elsevier Ltd. 保留所有权利。
Transforming growth factor (TGF)-beta signalling plays a dichotomous role in tumour progression, acting as a tumour suppressor early and as a pro-metastatic pathway in late-stages. There is accumulating evidence that advanced-stage tumours produce excessive levels of TGF-beta, which acts to promote tumour growth, invasion and colonisation of secondary organs. In light of the pro-metastasis function, many strategies are currently being explored to antagonise the TGF-beta pathway as a treatment for metastatic cancers. Strategies such as using large molecule ligand traps, reducing the translational efficiency of TGF-beta ligands using antisense technology, and antagonising TGF-beta receptor I/II kinase function using small molecule inhibitors are the most prominent methods being explored today. Administration of anti-TGF-beta therapies alone, or in combination with immunosuppressive or cytotoxic therapies, has yielded promising results in the preclinical and clinical settings. Despite these successes, the temporal- and context-dependent roles of TGF-beta signalling in cancer has made it challenging to define patient subgroups that are most likely to respond, and the therapeutic regimens that will be most effective in the clinic. Novel mouse models and diagnostic tools are being developed today to circumvent these issues, which may potentially expedite anti-TGF-beta drug development and clinical application. (C) 2010 Elsevier Ltd. All rights reserved.