Owing to the molecular complexity of cancer and the cost of therapy, researchers have begun looking to in vivo functional genomics to inform patient care. Unfortunately, xenographs of established tumour cell lines in immunodeficient mice fail to recapitulate many critical features of human primary tumours. By contrast, mouse models of cancer often faithfully recapitulate basic biology, tumour-microenvironment interactions, drug responses and therapy resistance similar to human disease. Thus, we established the co-clinical trial project, and in doing so developed the concept of the mouse hospital, whereby in vivo preclinical and early clinical studies are closely aligned, enabling in vivo testing of drugs in a multitude of cancer subtypes using mouse models, while minimizing the cost and time required to study responses in thousands of human patients. This approach can inform enrollment of patients in clinical trials, and can enable repositioning and/or repurposing of previously approved drugs.