Cancer stem cells and modeling cancer in the mouse

The complexity of cancer biology cannot be understood in all its depth solely with the study of human patients and the samples derived from them. These types of studies are undeniably essential, but the heterogeneity among human patients, together with the long latency of the disease and its usually delayed diagnosis, make it difficult to recapitulate all the phases of the disease from human studies. In this context, genetically engineered mouse models (GEMMs) of human cancer are essential tools for our understanding of the processes leading to the disease. The sophistication of the techniques allowing us to model cancer in mice has increased enormously over the last years, to the extent that we can now induce, study and manipulate the disease, its evolution and its response to treatment in a way that is not possible in humans. The identification of cancer stem cells (CSCs) as the only cells within the tumor with the capacity of propagating and maintaining the disease has added a new layer of complexity to our understanding of cancer. However, most of GEMMs generated and characterized to date have not being designed to take into account the existence of CSCs and their role in the disease generation, evolution and response to treatment. In this chapter we briefly revise the major milestones in the history of the generation of mouse models of cancer, and propose new strategies for the future, taking into consideration what we nowadays know about the hierarchical nature of tumors.