Cancer stem cells: how can we target them?
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/beta-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.
Ischenko
Ivan
I
Department of Surgery - Grosshadern Campus, Medical Center of the University of Munich, Marchioninistr. 15, D-81377 Munich, Germany. Ivan.Ischenko@med.uni-muenchen.de
Seeliger
Hendrik
H
Schaffer
Moshe
M
Jauch
Karl-Walter
KW
Bruns
Christiane J
CJ
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D002471:Cell Transformation, Neoplastic / Q000473:pathology; D006801:Humans; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D012680:Sensitivity and Specificity
D000970:Antineoplastic Agents