目前,癌症仍然是全球人类死亡的主要原因。肿瘤恶化包括多个事件,包括转移,治疗抗性和免疫逃避,所有这些都与表型可塑性密切相关,尤其是上皮间质可塑性(EMP)。具有EMP的肿瘤细胞表现为上皮-间质转化(EMT)三种状态,部分EMT,和间质-上皮转化,通过转录调控和一系列信号通路协调肿瘤细胞的表型转换和异质性,包括转化生长因子-β,Wnt/β-catenin,还有Notch.然而,由于EMP的复杂性,EMP的多样化过程仍未完全理解。在这次审查中,我们系统地总结生物学背景,EMP的调节机制以及EMP在治疗反应中的作用。我们还总结了一系列小分子抑制剂,免疫相关的治疗方法,以及针对EMP开发的联合疗法对EMP驱动的肿瘤恶化的突出作用。此外,我们探索基于EMP的肿瘤机制研究和治疗研究的潜在技术,这可能会爆发出强劲的前景。总的来说,我们阐明了EMP在肿瘤进展中的多方面,并提出了基于靶向EMP的癌症治疗方向.
Currently, cancer is still a leading cause of human death globally. Tumor deterioration comprises multiple events including metastasis, therapeutic resistance and immune evasion, all of which are tightly related to the phenotypic plasticity especially epithelial-mesenchymal plasticity (EMP). Tumor cells with EMP are manifest in three states as epithelial-mesenchymal transition (EMT), partial EMT, and mesenchymal-epithelial transition, which orchestrate the phenotypic switch and heterogeneity of tumor cells via transcriptional regulation and a series of signaling pathways, including transforming growth factor-β, Wnt/β-catenin, and Notch. However, due to the complicated nature of EMP, the diverse process of EMP is still not fully understood. In this review, we systematically conclude the biological background, regulating mechanisms of EMP as well as the role of EMP in therapy response. We also summarize a range of small molecule inhibitors, immune-related therapeutic approaches, and combination therapies that have been developed to target EMP for the outstanding role of EMP-driven tumor deterioration. Additionally, we explore the potential technique for EMP-based tumor mechanistic investigation and therapeutic research, which may burst vigorous prospects. Overall, we elucidate the multifaceted aspects of EMP in tumor progression and suggest a promising direction of cancer treatment based on targeting EMP.