Revisiting the dynamic cancer stem cell model: Importance of tumour edges

The lack of an effective treatment against cancer is not only due to its huge heterogeneity, but also to the fact that we don’t have an answer to the question on how cancer originates. Among the proposed models to explain the development of cancer, the hierarchical model has been widely accepted. Nevertheless, this model fails to explain several experimental observations such as the cancer stem cells (CSCs) location inside a tumour or the differences between primary and metastatic tumours. Moreover, increasing evidence shows that the CSC phenotype is not a rigid state. Here, we present a critical review on the assumed tumour development models emphasizing the relevance of the dynamic and changing nature of cancer and the CSCs population in which the tumour microenvironment plays a crucial role and we propose a new model of tumour origin that could have an impact on new therapeutic strategies.