Ismail Fatima, Winkler David A
CSIRO Materials Science & Engineering, Bag 10, Clayton South MDC VIC 3169 (Australia).
ChemMedChem. 2014 May;9(5):885-98. doi: 10.1002/cmdc.201400068. Epub 2014 Apr 23.
Cancers are among the most important and most difficult to treat diseases of the 21st century. Conventional therapies include surgery, immunotherapy, and radiotherapy, as well many forms of drug treatments such as tamoxifen and Gleevec. However, these forms of treatment often do not eradicate the cancer stem cells, only managing to decrease the size of the tumor, allowing the cancer to return. The cancer stem cell hypothesis stipulates that malignancy is maintained through self-renewal of cancer stem cells (CSCs), which generate rapidly dividing progeny that comprise the tumors, and that are largely untouched by conventional therapies. Evidence for the central role of CSCs in many tumors has provided a paradigm shift in the way cancer chemotherapy may be addressed. Recent discoveries regarding the nature of the stem cell niche, and the key signaling pathways involved in stem cell self-renewal and differentiation from regenerative medicine, have provided key information that facilitates selective targeting of CSCs by small-molecule drugs. The growing body of biochemical knowledge on the nature of CSCs, and differences between them and normal adult stem cells essential for maintaining organisms, has augmented the increasing number of small molecules shown to control normal and aberrant stem cells. Here, we review small-molecule approaches to the selective targeting of CSCs.
癌症是21世纪最重要且最难治疗的疾病之一。传统疗法包括手术、免疫疗法和放射疗法，以及许多形式的药物治疗，如他莫昔芬和格列卫。然而，这些治疗形式往往无法根除癌症干细胞，只能设法减小肿瘤的大小，从而使癌症复发。癌症干细胞假说规定，恶性肿瘤是通过癌症干细胞（CSCs）的自我更新来维持的，这些干细胞产生快速分裂的子代细胞，构成肿瘤，而传统疗法对它们基本无效。癌症干细胞在许多肿瘤中起核心作用的证据，为癌症化疗的应对方式带来了范式转变。最近关于干细胞生态位的性质，以及再生医学中涉及干细胞自我更新和分化的关键信号通路的发现，提供了关键信息，有助于小分子药物选择性地靶向癌症干细胞。关于癌症干细胞性质的生化知识不断增加，以及它们与维持生物体所必需的正常成体干细胞之间的差异，使得越来越多的小分子被证明可以控制正常和异常干细胞。在此，我们综述了选择性靶向癌症干细胞的小分子方法。
