Bhatia Sugandha, Monkman James, Toh Alan Kie Leong, Nagaraj Shivashankar H, Thompson Erik W
Institute of Health and Biomedical Innovation and School of Biomedical Sciences, Queensland University of Technology, Brisbane, Australia.
Translational Research Institute, Brisbane, Australia.
Biochem J. 2017 Sep 20;474(19):3269-3306. doi: 10.1042/BCJ20160782.
The concept of epithelial-mesenchymal plasticity (EMP), which describes the dynamic flux within the spectrum of phenotypic states that invasive carcinoma cells may reside, is being increasingly recognised for its role in cancer progression and therapy resistance. The myriad of events that are able to induce EMP, as well as the more recently characterised control loops, results in dynamic transitions of cancerous epithelial cells to more mesenchymal-like phenotypes through an epithelial-mesenchymal transition (EMT), as well as the reverse transition from mesenchymal phenotypes to an epithelial one. The significance of EMP, in its ability to drive local invasion, generate cancer stem cells and facilitate metastasis by the dissemination of circulating tumour cells (CTCs), highlights its importance as a targetable programme to combat cancer morbidity and mortality. The focus of this review is to consolidate the existing knowledge on the strategies currently in development to combat cancer progression via inhibition of specific facets of EMP. The prevalence of relapse due to therapy resistance and metastatic propensity that EMP endows should be considered when designing therapy regimes, and such therapies should synergise with existing chemotherapeutics to benefit efficacy. To further improve upon EMP-targeted therapies, it is imperative to devise monitoring strategies to assess the impact of such treatments on EMP-related phenomenon such as CTC burden, chemosensitivity/-resistance and micrometastasis in patients.
上皮-间质可塑性（EMP）的概念描述了侵袭性癌细胞可能处于的表型状态范围内的动态变化，其在癌症进展和治疗耐药性中的作用正日益受到认可。能够诱导EMP的众多事件以及最近发现的控制回路，导致癌细胞通过上皮-间质转化（EMT）动态转变为更具间质样的表型，以及从间质表型逆向转变为上皮表型。EMP在驱动局部侵袭、产生癌症干细胞以及通过循环肿瘤细胞（CTC）的播散促进转移方面的重要性，凸显了其作为对抗癌症发病率和死亡率的可靶向程序的重要性。本综述的重点是整合目前正在开发的通过抑制EMP的特定方面来对抗癌症进展的策略的现有知识。在设计治疗方案时，应考虑到EMP赋予的治疗耐药性和转移倾向导致的复发率，此类疗法应与现有化疗药物协同作用以提高疗效。为了进一步改进针对EMP的疗法，必须设计监测策略，以评估此类治疗对患者中与EMP相关现象（如CTC负荷、化学敏感性/耐药性和微转移）的影响。
