Cancers 2011, 3(1), 1405-1425; doi:10.3390/cancers3011405
Review

Breast Cancer-Initiating Cells: Insights into Novel Treatment Strategies

Received: 14 January 2011; in revised form: 17 February 2011 / Accepted: 2 March 2011 / Published: 16 March 2011
(This article belongs to the Special Issue Cancer Stem Cells)
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract: There is accumulating evidence that breast cancer may arise from mutated mammary stem/progenitor cells which have been termed breast cancer-initiating cells (BCIC). BCIC identified in clinical specimens based on membrane phenotype (CD44+/CD24/low and/or CD133+ expression) or enzymatic activity of aldehyde dehydrogenase 1 (ALDH1+), have been demonstrated to have stem/progenitor cell properties, and are tumorigenic when injected in immunocompromized mice at very low concentrations. BCIC have also been isolated and in vitro propagated as non-adherent spheres of undifferentiated cells, and stem cell patterns have been recognized even in cancer cell lines. Recent findings indicate that aberrant regulation of self renewal is central to cancer stem cell biology. Alterations in genes involved in self-renewal pathways, such as Wnt, Notch, sonic hedgehog, PTEN and BMI, proved to play a role in breast cancer progression. Hence, targeting key elements mediating the self renewal of BCIC represents an attractive option, with a solid rationale, clearly identifiable molecular targets, and adequate knowledge of the involved pathways. Possible concerns are related to the poor knowledge of tolerance and efficacy of inhibiting self-renewal mechanisms, because the latter are key pathways for a variety of biological functions and it is unknown whether their interference would kill BCIC or simply temporarily stop them. Thus, efforts to develop BCIC-targeted therapies should not only be focused on interfering on self-renewal, but could seek to identify additional molecular targets, like those involved in regulating EMT-related pathways, in reversing the MDR phenotype, in inducing differentiation and controlling cell survival pathways.
Keywords: breast cancer-initiating cells; self-renewal pathways; survival pathways; prognosis; drug resistance, drug targets
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MDPI and ACS Style

Santilli, G.; Binda, M.; Zaffaroni, N.; Daidone, M.G. Breast Cancer-Initiating Cells: Insights into Novel Treatment Strategies. Cancers 2011, 3, 1405-1425.

AMA Style

Santilli G, Binda M, Zaffaroni N, Daidone MG. Breast Cancer-Initiating Cells: Insights into Novel Treatment Strategies. Cancers. 2011; 3(1):1405-1425.

Chicago/Turabian Style

Santilli, Guido; Binda, Mara; Zaffaroni, Nadia; Daidone, Maria Grazia. 2011. "Breast Cancer-Initiating Cells: Insights into Novel Treatment Strategies." Cancers 3, no. 1: 1405-1425.

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