肿瘤干细胞及其治疗抗性

Cancer stem cells and their therapy resistance

肿瘤是由处于不同发育阶段、形态及功能各异的细胞群体构成的"类器官",其中多数细胞可发生分化,而极少数细胞则维持未分化状态,被称为肿瘤干细胞。正常干细胞的自我更新、分化和增殖受其调控机制的严格控制,以维持体内各组织、器官的稳态,而肿瘤干细胞则具有恶性增殖的能力,经过不同形式的自我更新式分裂,产生并扩增具有不同分化表型、独特形态的异质性肿瘤细胞。大量的研究表明,常规治疗虽可杀灭大部分增殖活跃的肿瘤细胞,而肿瘤干细胞通常处于相对静止状态,并表达高水平的多药耐药基因,具有很强的药物抗性及DNA损伤修复能力,因而能成功地逃逸化疗、放疗的杀伤。残存的肿瘤干细胞侵袭、转移能力更强,成为肿瘤复发和转移的"祸根"。本文将综述近年来抗肿瘤治疗与肿瘤干细胞研究的新进展,讨论肿瘤干细胞表型特征、抗肿瘤治疗与肿瘤干细胞富集、肿瘤干细胞信号调控机制以及靶向肿瘤干细胞治疗的新理念。

Malignant tumor is a complex organ-like structure constituted by a morphologically and functionally heterogeneous population of cells at different developmental stages. The majority of cells are destined to differentiate and a minority subset of cell population, called cancer stem cells （CSCs）, is maintained in the undifferentiated state. Normally, the ability of stem cells to undergo self-renewal, differentiation and proliferation is tightly controlled by the regulatory mechanisms in order to maintain tissue and organ homeostasis in the body. However, CSCs with the capacity for malignant proliferation undergo various types of division and generate tumor cells with different phenotypes and distinct morphologies. Numerous studies demonstrate that conventional therapeutics efficiently eradicate rapidly dividing cells, but quiescent CSCs that highly express multidrug resistance genes appear intrinsically resistant to conventional chemotherapy and DNA damage, allowing themselves to successfully evade both chemotherapy and radiation. Residual CSCs with enhanced migratory and invasive capacities are responsible for tumor relapse and metastases. Here we review the progress in anti-tumor therapy and discuss the phenotypic characteristics of CSCs, enrichment of CSCs associated with anti-tumor therapy, the signal transduction of CSCs and novel CSC-targeting therapies.