title: The right time, the right place: will targeting human cancer-associated mutations to the mouse provide the perfect preclinical model?
abstract: Over the past 10 years the realisation that genetic mouse models of cancer may play a key role in preclinical drug development has gained strong momentum. Moreover sequencing studies of human tumours have provided key insights into the mutational complexity of epithelial cancer, unleashing important clues for researchers to generate accurate genetically engineered mouse (GEM) models of cancer. Thus by targeting multiple cancer associated human mutations to the appropriate murine epithelia, mice develop tumours that more closely recapitulate the human disease. As a number of excellent models now exist, the next 5-10 years will ascertain whether these models will predict response of human cancer to intervention. If so they might become the 'gold standard' where all drugs are required to be tested in mouse models of disease before proceeding into the patient. However, although this principle is very attractive, it is relatively untested and here, using examples of prevalent human cancers, we will review the latest data on preclinical GEM studies and comment on what challenges are left to overcome.
authors.affiliation: The Beatson Institute for Cancer Research, Switchback Road, Glasgow, G61 1BD, UK.
authors.forename: Karen
authors.initials: K
authors.lastname: Blyth
authors.forename: Jennifer P
authors.initials: JP
authors.lastname: Morton
authors.forename: Owen J
authors.initials: OJ
authors.lastname: Sansom
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology