Next-generation in vivo modeling of human cancers

Animal models of human cancers played a major role in our current understanding of tumor biology. In pre-clinical oncology, animal models empowered drug target and biomarker discovery and validation. In turn, this resulted in improved care for cancer patients. In the quest for understanding and treating a diverse spectrum of cancer types, technological breakthroughs in genetic engineering and single cell "omics" offer tremendous potential to enhance the informative value of pre-clinical models. Here, I review the state-of-the-art in modeling human cancers with focus on animal models for human malignant gliomas. The review highlights the use of glioma models in dissecting mechanisms of tumor initiation, in the retrospective identification of tumor cell-of-origin, in understanding tumor heterogeneity and in testing the potential of immuno-oncology. I build on the deep review of glioma models as a basis for a more general discussion of the potential ways in which transformative technologies may shape the next-generation of pre-clinical models. I argue that refining animal models along the proposed lines will benefit the success rate of translation for pre-clinical research in oncology.