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Targeting Breast Cancer Stem Cells

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Breast Cancer Stem Cells & Therapy Resistance

Part of the book series: SpringerBriefs in Stem Cells ((BRIEFSSTEM))

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Abstract

Some therapies that target the stemness of breast CSCs have been developed, all of which aim to stimulate differentiation of breast CSCs into breast non-CSCs, thus eliminating their capacity for self-renewal. Once breast CSCs lose the capacity for self-renewal, they can also lose their resistance to radiotherapy or chemotherapy and ability to invade. In theory, CSC targeted therapy can attack CSCs so effectively that the tumors degenerate. In contrast, traditional cancer therapies attack and kill tumor cells but not CSCs; thus, these tumors shrink but subsequently grow back. Chemo- or radio-resistance, which markedly impairs the efficacy of cancer therapy, involves anti-apoptotic signal transduction pathways that prevent cell death. To date, some molecular mechanisms have been identified that may account for the resistance of breast CSCs to cytotoxic agents. Over-expression of some proteins relating to multidrug resistance has been recognized in breast CSCs. Breast CSCs may also strongly express anti-apoptotic proteins such as survivin and B-cell lymphoma extra-large. Moreover, the efficiency of DNA repair is greater in breast CSCs, which may make them more resistant to traditional agents.

Self-renewal pathways play vital roles in stem cells, in general, including in CSCs. Some signaling pathways, such as Wnt, Notch, and Hedgehog, are expressed strongly in stem cells. These pathways can help breast CSCs to maintain their phenotypes during tumor growth (so-called self-renewal). In fact, some experiments have shown that when they are dysregulated in mammary glands, the affected mice develop breast cancer. Notably, these pathways are dysregulated in almost human BCSC lines. One of the pathways most strongly related to self-renewal is the Her2-signaling pathway, a pathway that many therapies have targeted. These agents were developed to suppress Her2-overexpressing breast cancer and include trastuzumab and lapatinib. In vivo, trastuzumab and lapatinib can improve progression-free survival and overall survival of patients with advanced disease and in vitro trastuzumab has been shown to reduce breast CSC numbers. However, these agents also have some limitations; in particular, almost 50 % of patients who respond to HER2-targeted agents relapse within one year.

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  1. Animal Physiology and Biotechnology, Vietnam National University of Science, Ho Chi Minh City, Vietnam

    Phuc Van Pham

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Van Pham, P. (2015). Targeting Breast Cancer Stem Cells. In: Breast Cancer Stem Cells & Therapy Resistance. SpringerBriefs in Stem Cells. Springer, Cham. https://doi.org/10.1007/978-3-319-22020-8_6

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