Chumsri Saranya, Burger Angelika M
University of Maryland School of Medicine, Marlene and Stewart Greenebaum Cancer Center, North Hospital S9D10, 22 South Greene Street, Baltimore, MD 21201, USA.
Curr Opin Mol Ther. 2008 Aug;10(4):323-33.
An increased understanding of stem-cell biology at the molecular level, as well as the isolation and characterization of a rare subset of cells with tumor-initiating properties from several human tumor types, have renewed interest in the exploitation of cancer stem cells (CSCs) as therapeutic targets. Although CSCs share various characteristics with normal stem cells, including self-renewal, asymmetric cell division, indefinite proliferative capacity, and self-protection mechanisms, they also contain unique and disease-specific features suitable for exploitation as therapeutic targets. Several existing anticancer agents and experimental therapeutics can inhibit pathways critical to CSC maintenance, and could, therefore, be utilized to eradicate CSCs. In this review, general and tumor-type specific cancer-stem-cell targets are highlighted. In addition, known inhibitors of these targets that could be utilized in the design of clinical protocols together with conventional cytotoxics as debulking agents are described.
在分子水平上对干细胞生物学的深入理解,以及从多种人类肿瘤类型中分离和鉴定出具有肿瘤起始特性的罕见细胞亚群,重新激发了人们将癌症干细胞(CSCs)作为治疗靶点加以利用的兴趣。尽管癌症干细胞与正常干细胞具有多种共同特征,包括自我更新、不对称细胞分裂、无限增殖能力和自我保护机制,但它们也具有适合作为治疗靶点加以利用的独特且疾病特异性特征。几种现有的抗癌药物和实验性疗法可以抑制对癌症干细胞维持至关重要的信号通路,因此可用于根除癌症干细胞。在这篇综述中,突出了一般的和肿瘤类型特异性的癌症干细胞靶点。此外,还描述了这些靶点的已知抑制剂,它们可与传统细胞毒性药物作为减瘤剂一起用于临床方案的设计。