Trumpp Andreas, Wiestler Otmar D
Genetics and Stem Cell Laboratory, Ecole Polytechnique Fédérale de Lausanne, Swiss Institute for Experimental Cancer Research, School of Life Science, Epalinges, Switzerland.
Nat Clin Pract Oncol. 2008 Jun;5(6):337-47. doi: 10.1038/ncponc1110. Epub 2008 Apr 22.
Classical antineoplastic treatments such as chemotherapy or radiation can efficiently eradicate the majority of proliferating and genetically unstable malignant cells within neoplastic lesions. There is increasing evidence, however, that these regimens frequently fail to eliminate a minor subpopulation of resistant tumor cells that have distinct features of somatic stem cells. These serve as a reservoir for disease recurrence, and are the origin of metastatic growth. These so-called cancer stem cells (CSCs) or cancer-initiating cells represent often a rare, highly self-renewing population within the tumor mass, which is thought to be the only one required for both initiation and maintenance of disease. Tumor-cell populations enriched for CSC activity were originally identified in leukemias, but have now also been uncovered in a number of solid cancers. Their marked resistance towards classical antitumor regimens is mediated by the combination of several critical features, including relative dormancy, efficient DNA repair, high expression of multidrug-resistance-type membrane transporters and protection by a hypoxic niche environment. We review the concept of CSCs with particular emphasis on the mechanism of therapy resistance, and discuss potential future therapeutic interventions with the goal of specifically eliminating CSCs in a clinical setting.
传统的抗肿瘤治疗方法，如化疗或放疗，能够有效地根除肿瘤病灶内大多数增殖且基因不稳定的恶性细胞。然而，越来越多的证据表明，这些治疗方案常常无法清除一小部分具有体细胞干细胞独特特征的耐药肿瘤细胞。这些细胞是疾病复发的根源，也是转移生长的起源。这些所谓的癌症干细胞（CSCs）或癌症起始细胞通常在肿瘤组织中是一个罕见的、高度自我更新的群体，被认为是引发和维持疾病所必需的唯一细胞群体。最初在白血病中发现了富含CSC活性的肿瘤细胞群体，但现在在多种实体癌中也已被发现。它们对传统抗肿瘤治疗方案具有显著抗性，这是由多种关键特征共同作用介导的，包括相对静止、高效的DNA修复、多药耐药型膜转运蛋白的高表达以及低氧微环境的保护。我们回顾了癌症干细胞的概念，特别强调了治疗抗性机制，并讨论了未来可能的治疗干预措施，目标是在临床环境中特异性地清除癌症干细胞。
