The lack of an effective treatment against cancer is not only due to its huge heterogeneity and complexity, but also to the fact that we do not entirely understand this disorder, highlighting the question of how cancer originates. Among the proposed models to explain the development of cancer, the hierarchical model has been widely accepted as a result of the extensive experimental data about the cancer stem cells (CSCs). Nevertheless, this model fails to explain several experimental observations such as the CSCs location mainly in the edges of solid tumour masses or the differences between primary and metastatic tumours. Moreover, increasing evidence shows that the CSC phenotype is not a rigid state and that it can be acquired by well-differentiated cancerous cells. In the present study, we present a critical review on the assumed tumour development models emphasizing the relevance of the dynamic and changing nature of malignant phenotype and the CSCs population in which the tumour microenvironment plays a crucial role. We also propose a new model of tumour origin and development that could have an impact on new therapeutic strategies.

Dr. Pablo Hernández-Camarero Degree in Biochemistry. University of Granada, Spain (2011-2015), Master in Translational Research and Personalized Medicine. University of Granada, Spain (2015-2016),3rd PhD-student in the Department of Health Science, University of Jaén, Spain (2017).