Journal of Stem Cell and Regenerative Biology | Volume 2 | Issue 3 | 2016-12-20

Breast cancer stem cells and opportunities for therapeutics

Sachin Kumar Deshmukh

Keywords: Cancer stem cells, Breast cancer stem cells, Therapeutics

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Cancer stem cells (CSCs) are in the scientific limelight from past few years in the studies involving cancer initiation, progression, and therapy resistance. Stem cells follow asymmetric division that generates un-identical cell types during embryogenesis which ultimately helps CSCs to maintain homeostasis. The CSCs are believed to significantly contribute to the tumor heterogeneity that is recognized by the existence of the diverse population of cells within the tumor. Breast cancer (BC) is one of the most heterogeneous tumors and leading cause of cancer-related deaths worldwide. Breast cancer stem cells (BCSCs) have been implicated in therapy resistance that influences the overall outcome of this disease. The BCSCs phenotype determined to unresponsive for chemotherapy and paclitaxel treatment were found to induce the BCSCs phenotype in BC cells in vitro . In addition, BCSCs escape chemotherapy and promote drug resistance by accumulate mutation, and accelerateself-renewal process after drug delivery [1] . Interestingly, enhanced expression of CD44+/CD24-, a CSCs marker was determined in primary tumors after chemotherapy [2] . Further, resistance to endocrine therapy was associated with elevated BCSCs [3] . In addition, the BCSCs were demonstrated to be resistance to radiotherapy in animal model [4] . Altogether, this evidence suggests that BCSC promotes therapy resistance and targeting this population can be an effective therapeutic strategy for BC. The BCSC demonstrate resistant to conventional therapies due to elevated membrane transport, ROS scavenging systems, altered mechanisms of DNA repair, and the ability to detoxify cytotoxic drugs. Moreover, several transcription factors, tumor suppressor genes, and signaling pathways, helps these cells to maintain and amplify a state of stemness. In addition, extensive crosstalk between BCSCs and their microenvironments influence CSCs function. Understanding the molecular mechanisms responsible for CSCs resistance phenotype which enhance drug efflux transporters, DNA repair machinery and antiapoptotic proteins expression can be beneficial to target these populations. Several signaling pathways such as Wnt, Notch, NF- B, Hedgehog, and EGFR have been implicated in the activity of malignant stem cell. The role of micro RNAs (miRNAs) are also implicated in the development of BCSCs. Several miRNAs such as let-7, miR-200, miR-183, miR-214, miR-221- 222 and miR-142, and their clusters found to be differentially expressed between human BCSCs and non-tumorigenic cancer cells [5] . These miRNAs target the genes and pathways crucial for apoptosis, stem cell maintenance, self-renewal, and epithelial-to-mesenchymal transition. Thus, understanding the role of miRNAs in the induction of BCSCs is important to counter this disease. Several therapeutic agents have been developed to eliminate or inhibit the BCSCs including disulfiram [6] , curcumin [7] , salinomycin [8] , chloroquine [9] , and siRNA [10] . Further, several nano carriers based delivery system is also employed to target the BCSCs. However, only limited success have been achieved in in vivo conditions. To advance anti-BCSCs targeted therapy, a better understanding of BCSCs microenvironment is crucial. Moreover, identification of genetic/molecular markers that are more specific to BCSCs may help to optimize the BCSCs targeting strategies. References 1. Dean, M., Fojo, T., Bates, S. Tumour stem cells and drug resistance. (2005) Nat Rev Cancer 5(4): 275 284. 2. Li, X., Lewis, M.T., Huang, J., et al. Intrinsic resistance of tumorigenic breast cancer cells to chemotherapy. (2008) J Natl Cancer Inst 100(9): 672 679. 3. Piva, M., Domenici, G., Iriondo, O., et al. Sox2 promotes tamoxifen resistance in breast cancer cells. (2014) EMBO Mol Med 6(1): 66 79. 4. 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