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

Breast Cancer-Initiating Cells: Insights into Novel Treatment Strategies

Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS-Istituto Nazionale dei Tumori, Via Amadeo 42, Milan 20133, Italy
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Received: 14 January 2011 / Revised: 17 February 2011 / Accepted: 2 March 2011 / Published: 16 March 2011
(This article belongs to the Special Issue Cancer Stem Cells)
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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 breast cancer-initiating cells; self-renewal pathways; survival pathways; prognosis; drug resistance, drug targets
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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

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