Cancer Prevention Research Program, Palindrome Liaisons Consultants, Montvale, NJ 07645-1559, USA.
Int J Mol Sci. 2022 Aug 17;23(16):9223. doi: 10.3390/ijms23169223.
The progression of the early stages of female breast and colon cancer to metastatic disease represents a major cause of mortality in women. Multi-drug chemotherapy and/or pathway selective targeted therapy are notable for their off-target effects and are associated with spontaneous and/or acquired chemotherapy resistance and the emergence of premalignant chemo-resistant cancer-initiating stem cells. The stem cell populations are responsible for the evolution of therapy-resistant metastatic disease. These limitations emphasize an unmet need to develop reliable drug-resistant cancer stem cell models as novel experimental approaches for therapeutic alternatives in drug discovery platforms. Drug-resistant stem cell models for breast and colon cancer subtypes exhibit progressive growth in the presence of cytotoxic chemo-endocrine therapeutics. The resistant cells exhibit upregulated expressions of stem cell-selective cellular and molecular markers. Dietary phytochemicals, nutritional herbs and their constituent bioactive compounds have documented growth inhibitory efficacy for cancer stem cells. The mechanistic leads for the stem cell-targeted efficacy of naturally occurring agents validates the present experimental approaches for new drug discovery as therapeutic alternatives for therapy-resistant breast and colon cancer. The present review provides a systematic discussion of published evidence on (i) conventional/targeted therapy for breast and colon cancer, (ii) cellular and molecular characterization of stem cell models and (iii) validation of the stem cell models as an experimental approach for novel drug discovery of therapeutic alternatives for therapy-resistant cancers.
女性乳腺癌和结肠癌早期阶段向转移性疾病的进展是导致女性死亡的主要原因之一。多药化疗和/或通路选择性靶向治疗以其脱靶效应为特征，与自发性和/或获得性化疗耐药以及癌前化疗耐药起始干细胞的出现有关。干细胞群体是导致治疗耐药转移性疾病进化的原因。这些局限性强调了开发可靠的耐药性癌症干细胞模型的迫切需求，作为药物发现平台中治疗替代方案的新实验方法。用于乳腺癌和结肠癌亚型的耐药性干细胞模型在细胞毒性化疗内分泌治疗存在的情况下表现出持续生长。耐药细胞表现出上调的干细胞选择性细胞和分子标志物的表达。植物化学物质、营养草药及其组成的生物活性化合物已被证明对癌症干细胞具有生长抑制作用。天然存在的药物针对干细胞的作用机制为新的药物发现提供了实验方法，为治疗耐药性乳腺癌和结肠癌提供了治疗替代方案。本综述系统地讨论了关于（i）乳腺癌和结肠癌的常规/靶向治疗，（ii）干细胞模型的细胞和分子特征，以及（iii）作为治疗耐药性癌症的新型药物发现治疗替代方案的实验方法验证的已发表证据。
