新型治疗策略：靶向结直肠癌中的上皮-间充质转化。

Novel therapeutic strategies: targeting epithelial-mesenchymal transition in colorectal cancer.

机构信息

West China School of Medicine, Sichuan University, Chengdu, China; Radcliffe Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK; University of Oxford-Sichuan University Huaxi Joint Centre for Gastrointestinal Cancer, Oxford, UK; Department of Oncology, West China Hospital, Sichuan University, Chengdu, China.

Radcliffe Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK; University of Oxford-Sichuan University Huaxi Joint Centre for Gastrointestinal Cancer, Oxford, UK.

出版信息

Lancet Oncol. 2021 Aug;22(8):e358-e368. doi: 10.1016/S1470-2045(21)00343-0.

DOI:10.1016/S1470-2045(21)00343-0

PMID:34339656

Abstract

Epithelial-mesenchymal transition (EMT) is a process during which cells lose their epithelial characteristics, for instance apical-basal cell polarity and cell-cell contact, and gain mesenchymal properties, such as increased motility. In colorectal cancer, EMT has an important role in tumour progression, metastasis, and drug resistance. There has been accumulating evidence from preclinical and early clinical studies that show that EMT markers might serve as outcome predictors and potential therapeutic targets in colorectal cancer. This Review describes the fundamentals of EMT, including biology, newly partial EMT, and associated changes. We also provide a comprehensive summary of therapeutic compounds capable of targeting EMT markers, including drugs in preclinical and clinical trials and those with repurpose potential. Lastly, we explore the obstacles of EMT bench-to-bedside drug development.

摘要

上皮-间充质转化（EMT）是一个细胞失去上皮特征，例如顶端-基底细胞极性和细胞-细胞接触，并获得间充质特性的过程，如增加迁移性。在结直肠癌中，EMT 在肿瘤进展、转移和耐药性中起着重要作用。越来越多的临床前和早期临床研究证据表明，EMT 标志物可能作为结直肠癌的预后预测因子和潜在的治疗靶点。这篇综述描述了 EMT 的基础，包括生物学、部分 EMT 以及相关的变化。我们还全面总结了能够靶向 EMT 标志物的治疗化合物，包括临床前和临床试验中的药物以及具有再利用潜力的药物。最后，我们探讨了 EMT 从实验室到临床的药物开发所面临的障碍。