Tumoral stem cell reprogramming as a driver of cancer: Theory, biological models, implications in cancer therapy

Cancer is a clonal malignant disease originated in a single cell and characterized by the accumulation of partially differentiated cells that are phenotypically reminiscent of normal stages of differentiation. According to current models, therapeutic strategies that block oncogene activity are likely to selectively target tumor cells. However, recent evidences have revealed that cancer stem cells could arise through a tumor stem cell reprogramming mechanism, suggesting that genetic lesions that initiate the cancer process might be dispensable for tumor progression and maintenance. This review addresses the impact of these results toward a better understanding of cancer development and proposes new approaches to treat cancer in the future.Research in ISG group is partially supported by FEDER and by MICINN (SAF2012-32810), by MEC OncoBIO Consolider-Ingenio 2010 (Ref. CSD2007-0017), by NIH grant (R01 CA109335-04A1), the ARIMMORA Project (FP7-ENV-2011, European Union Seventh Framework Program), by Junta de Castilla y Leon (BIO/SA06/13) and by proyecto en red de investigación en celulas madre tumorales supported by Obra Social Kutxa y Conserjería de Sanidad de la Junta de Castilla y Leon. ISG is an API lab of the EuroSyStem project and a partner within the Marie Curie Initial Training Network DECIDE (decision-making within cells and differentiation entity therapies). LRR was supported by FSE-Conserjería de Educación de la Junta de Castilla y León (CSI020-12).Peer Reviewe