Jonckheere Sven, Adams Jamie, De Groote Dominic, Campbell Kyra, Berx Geert, Goossens Steven
Cancer Research Institute Ghent (CRIG), Ghent University, Ghent, Belgium.
Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
Cells Tissues Organs. 2022;211(2):157-182. doi: 10.1159/000512218. Epub 2021 Jan 5.
Metastasis is the spread of cancer cells from the primary tumour to distant sites and organs throughout the body. It is the primary cause of cancer morbidity and mortality, and is estimated to account for 90% of cancer-related deaths. During the initial steps of the metastatic cascade, epithelial cancer cells undergo an epithelial-mesenchymal transition (EMT), and as a result become migratory and invasive mesenchymal-like cells while acquiring cancer stem cell properties and therapy resistance. As EMT is involved in such a broad range of processes associated with malignant transformation, it has become an increasingly interesting target for the development of novel therapeutic strategies. Anti-EMT therapeutic strategies could potentially not only prevent the invasion and dissemination of cancer cells, and as such prevent the formation of metastatic lesions, but also attenuate cancer stemness and increase the effectiveness of more classical chemotherapeutics. In this review, we give an overview about the pros and cons of therapies targeting EMT and discuss some already existing candidate drug targets and high-throughput screening tools to identify novel anti-EMT compounds.
转移是指癌细胞从原发性肿瘤扩散到全身远处的部位和器官。它是癌症发病和死亡的主要原因,据估计占癌症相关死亡的90%。在转移级联反应的初始阶段,上皮癌细胞经历上皮-间质转化(EMT),结果变成具有迁移性和侵袭性的间质样细胞,同时获得癌症干细胞特性和治疗抗性。由于EMT参与了与恶性转化相关的如此广泛的过程,它已成为开发新型治疗策略越来越有趣的靶点。抗EMT治疗策略不仅有可能预防癌细胞的侵袭和扩散,从而防止转移病灶的形成,而且还能减弱癌症干性并提高更传统化疗的有效性。在这篇综述中,我们概述了针对EMT的治疗方法的优缺点,并讨论了一些现有的候选药物靶点和高通量筛选工具,以识别新型抗EMT化合物。