National Centre for Cell Science, SP Pune University Campus, Pune 411007, India.
Int J Biochem Cell Biol. 2019 Feb;107:38-52. doi: 10.1016/j.biocel.2018.12.001. Epub 2018 Dec 5.
Breast cancer remains to be a dreadful disease even with several advancements in radiation and chemotherapies, owing to the drug resistance and tumor relapse caused by breast cancer stem cells. Cancer stem cells are a minute population of cells of solid tumors which show self-renewal and differentiation properties as well as tumorigenic potential. Several signaling pathways including Notch, Hippo, Wnt and Hedgehog and tumor-stroma exchanges play a critical role in the self-renewal and differentiation of cancer stem cells in breast cancer. Cancer stem cells can grow anchorage-independent manner so they disseminate to different parts of the body to form secondary tumors. Cancer stem cells promote angiogenesis by dedifferentiating to endothelial cells as well as secreting proangiogenic and angiogenic factors. Moreover, multidrug resistance genes and drug efflux transporters expressed in breast cancer stem cells confer resistance to various conventional chemotherapeutic drugs. Indeed, these therapies are recognised to enhance the percent of cancer stem cell population in tumors leading to cancer relapse with increased aggressiveness. Hence, devising the therapeutic interventions to target cancer stem cells would be useful in increasing patients' survival rates. In addition, targeting the self-renewal pathways and tumor-stromal cross-talk helps in eradicating this population. Reversal of the cancer stem cell-mediated drug resistance would increase the sensitivity to various conventional drugs for the effective management of breast cancer. In this review, we have discussed the cancer stem cell origin and their involvement in angiogenesis, metastasis and therapy-resistance. We have also summarized different therapeutic approaches to eradicate the same for the successful treatment of breast cancer.
即使在放射治疗和化学疗法方面取得了一些进展，乳腺癌仍然是一种可怕的疾病，这是由于乳腺癌干细胞引起的耐药性和肿瘤复发。癌症干细胞是实体瘤中一小部分具有自我更新和分化特性以及致瘤潜能的细胞。包括 Notch、Hippo、Wnt 和 Hedgehog 在内的几个信号通路以及肿瘤-基质交换在乳腺癌中癌症干细胞的自我更新和分化中起着关键作用。癌症干细胞可以以非锚定方式生长，因此它们可以扩散到身体的不同部位形成继发性肿瘤。癌症干细胞通过分化为内皮细胞以及分泌促血管生成和血管生成因子来促进血管生成。此外，乳腺癌干细胞中表达的多药耐药基因和药物外排转运蛋白赋予其对各种常规化疗药物的耐药性。事实上，这些疗法被认为会增加肿瘤中癌症干细胞群体的比例，导致癌症复发并增加侵袭性。因此，设计针对癌症干细胞的治疗干预措施将有助于提高患者的生存率。此外，靶向自我更新途径和肿瘤-基质相互作用有助于消除这种群体。逆转癌症干细胞介导的耐药性将提高对各种常规药物的敏感性，从而有效治疗乳腺癌。在这篇综述中，我们讨论了癌症干细胞的起源及其在血管生成、转移和耐药性中的作用。我们还总结了不同的治疗方法来根除这些细胞，以成功治疗乳腺癌。
