Cancer Prevention Research Program, Palindrome Liaisons Consultants, Montvale, NJ 07645-1559, USA.
Int J Mol Sci. 2022 Jun 24;23(13):7055. doi: 10.3390/ijms23137055.
Metastatic progression of female breast and colon cancer represents a major cause of mortality in women. Spontaneous/acquired resistance to conventional and targeted chemo-endocrine therapy is associated with the emergence of drug-resistant tumor-initiating cancer stem cell populations. The cancer-initiating premalignant stem cells exhibit activation of select cancer cell signaling pathways and undergo epithelial-mesenchymal transition, leading to the evolution of a metastatic phenotype. The development of reliable cancer stem cell models provides valuable experimental approaches to identify novel testable therapeutic alternatives for therapy-resistant cancer. Drug-resistant stem cell models for molecular subtypes of clinical breast cancer and for genetically predisposed colon cancer are developed by selecting epithelial cells that survive in the presence of cytostatic concentrations of relevant therapeutic agents. These putative stem cells are characterized by the expression status of select cellular and molecular stem cell markers. The stem cell models are utilized as experimental approaches to examine the stem-cell-targeted growth inhibitory efficacy of naturally occurring dietary phytochemicals. The present review provides a systematic discussion on (i) conceptual and experimental aspects relevant to the chemo-endocrine therapy of breast and colon cancer, (ii) molecular/cellular aspects of cancer stem cells and (iii) potential stem-cell-targeting lead compounds as testable alternatives against the progression of therapy-resistant breast and colon cancer.
女性乳腺癌和结肠癌的转移进展是女性死亡的主要原因之一。对常规和靶向化疗内分泌治疗的自发/获得性耐药与耐药肿瘤起始癌症干细胞群体的出现有关。起始性癌前干细胞表现出选择的癌细胞信号通路的激活，并经历上皮-间充质转化，导致转移表型的演变。可靠的癌症干细胞模型的发展为识别针对耐药性癌症的新型可测试治疗替代方案提供了有价值的实验方法。通过选择在相关治疗药物的细胞抑制浓度下存活的上皮细胞，开发了用于临床乳腺癌的分子亚型和遗传易感性结肠癌的耐药性干细胞模型。这些假定的干细胞的特征在于选择细胞和分子干细胞标志物的表达状态。干细胞模型被用作实验方法来研究天然存在的膳食植物化学物质对干细胞靶向生长抑制作用的疗效。本综述系统地讨论了（i）与乳腺癌和结肠癌的化疗内分泌治疗相关的概念和实验方面，（ii）癌症干细胞的分子/细胞方面，以及（iii）针对耐药性乳腺癌和结肠癌进展的潜在的干细胞靶向先导化合物作为可测试的替代方案。
