The path to metastatic mouse models of colorectal cancer

The study and comprehension of the molecular mechanisms underlying cancer biology strongly rely on mouse modeling. An ideal mouse model should have molecular, histopathological, and etiological characteristics as close as possible to those of the corresponding human tumors. Among solid tumors, colorectal cancer (CRC) is one of the malignancies that best suits reproduction in an animal model: it evolves through a progressive set of molecular events and is generally associated with a precise histopathology and a neat cataloging of stages and grades. The development of refined CRC mouse models over several decades has seen them recently evolve toward sophisticated systems that ever more closely approximate the human pathology, with different models addressing different human CRC subtypes. In particular, a metastatic CRC model has been seen as a holy grail in this field, and we describe in this review the path taken to achieve metastatic models and discuss the path forward.