Dave Bhuvanesh, Chang Jenny
Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA.
J Mammary Gland Biol Neoplasia. 2009 Mar;14(1):79-82. doi: 10.1007/s10911-009-9117-9. Epub 2009 Mar 4.
Cancer stem cells are resistant to current chemotherapy and radiation regimens available for breast cancer, making it imperative to study the mechanisms of resistance and development of therapeutic strategies that targets the tumor initiating cell population. One of the difficulties in identifying new drug targets has been that our current high throughput drug screens look for tumor shrinkage and do not incorporate the impact of compounds on the cancer stem cell population. In this review we discuss the literature on treatment resistance in breast cancer and the design of new clinical trials for test compounds which will allow us to determine both the reduction in tumor size and decrease in cancer stem cell population. In order to detect the effect of target compounds on cancer stem cells in a clinical setting, we will need to do multiple assays which include high throughput flow sorting analysis to determine the total number of CD44(+)/CD24(-/low)/Lin(-) and ALDH1 positive cells, as well as in-vitro mammosphere formation assay which is a functional assay dependent on the self renewal and anchorage independent growth properties of these cells.
癌症干细胞对目前用于乳腺癌的化疗和放疗方案具有抗性，因此必须研究抗性机制并开发针对肿瘤起始细胞群体的治疗策略。识别新药物靶点的困难之一在于，我们目前的高通量药物筛选着眼于肿瘤缩小，并未纳入化合物对癌症干细胞群体的影响。在这篇综述中，我们讨论了关于乳腺癌治疗抗性的文献以及用于测试化合物的新临床试验设计，这将使我们能够确定肿瘤大小的减小以及癌症干细胞群体的减少。为了在临床环境中检测目标化合物对癌症干细胞的影响，我们需要进行多种检测，包括高通量流式分选分析以确定CD44(+)/CD24(-/低)/Lin(-)和ALDH1阳性细胞的总数，以及体外乳腺球形成检测，这是一种依赖于这些细胞自我更新和非锚定依赖性生长特性的功能检测。
