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Cancer Stem Cells: How can we Target them?

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Abstract:

One of the most exciting concepts being explored in cancer research today is the idea of cancer stem cells. Evidence for the existence of such cells was first proposed for haematological malignancies and, more recently, for solid tumors, including breast, brain, colon and pancreatic cancer. The cancer stem cell hypothesis states that a minority of transformed stem cells, or progenitors with acquired self-renewal properties, are the source of tumor cell renewal and thereby determine the behaviour of tumors, including proliferation, spreading and response to chemo- and radiotherapy. Indeed, just as somatic stem cells may be resistant to the induction of apoptosis by cytotoxic agents and radiation therapy, cancer stem cells may display increased resistance to these agents as compared with the more differentiated cells that comprise the mass of tumors. More specifically, the reactivation of varied developmental signalling cascades (epidermal growth factor (EGF)/EGFR, stem cell factor (SCF)/KIT, sonic hedgehog, Notch, and/or Wnt/β-catenin) combined with the increased DNA repair mechanisms and ABC transporter-mediated drug efflux in cancer stem cells may be responsible for their resistance to conventional therapies. Furthermore, changes in the local microenvironment of cancer stem cells may also influence their behaviour. Thus, the molecular targeting of such highly tumorigenic cancer cells must be considered for improving the efficacy of the current anti-cancer strategies with the aim to sensitize tumors toward conventional therapies and effectively abrogate tumorigenesis. This review provides a summary of some developments in the field of cancer stem cell targeting and highlights aspects where it could be of help in the drug discovery process.

Keywords: Oncogenesis; cancer progenitor cells; cancer stem cell targeted therapy; cancer stem cells; chemoresistance; differentiation; self-renewal

Document Type: Research Article

DOI: http://dx.doi.org/10.2174/092986708786848541

Affiliations: Department of Surgery - Grosshadern Campus, Medical Center of the University of Munich, Marchioninistr. 15, D-81377 Munich, Germany.

Publication date: December 1, 2008

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.

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