1. ¹LEXOR (Laboratory for Experimental Oncology and Radiobiology), Center for Experimental Molecular Medicine, Academic Medical Center (AMC), Amsterdam, The Netherlands
2. ²Department of Surgical and Oncological Sciences, Cellular and Molecular Pathophysiology Laboratory, University of Palermo, Palermo, Italy

Correspondence: JP Medema, CEMM Room G2-131, Academic Medical Center (AMC), Laboratory for Experimental Oncology and Radiobiology LEXOR, Meibergdreef 9, Amsterdam 1105 AZ, The Netherlands. Tel: +31 20 566 7777; Fax: +31 20 697 7192; E-mail: j.p.medema@amc.nl

Received 5 December 2007; Revised 4 January 2008; Accepted 7 January 2008; Published online 15 February 2008.

Abstract

Cancer has long been viewed as an exclusively genetic disorder. The model of carcinogenesis, postulated by Nowell and Vogelstein, describes the formation of a tumor by the sequential accumulation of mutations in oncogenes and tumor suppressor genes. In this model, tumors are thought to consist of a heterogeneous population of cells that continue to acquire new mutations, resulting in a highly dynamic process, with clones that out compete others due to increased proliferative or survival capacity. However, novel insights in cancer stem cell research suggest another layer of complexity in the process of malignant transformation and preservation. It has been reported that only a small fraction of the cancer cells in a malignancy have the capacity to propagate the tumor upon transplantation into immuno-compromised mice. Those cells are termed 'cancer stem cells' (CSC) and can be selected based on the expression of cell surface markers associated with immature cell types. In this review, we will critically discuss these novel insights in CSC-related research. Where possible we integrate these results within the genetic model of cancer and illustrate that the CSC model can be considered an extension of the classic genetic model rather than a contradictory theory. Finally, we discuss some of the most controversial issues in this field.