The Right Time, the Right Place: Will Targeting Human Cancer-Associated Mutations to the Mouse Provide the Perfect Preclinical Model?

Curr Opin Genet Dev. 2012 Feb;22(1):28-35. doi: 10.1016/j.gde.2012.02.009. Epub 2012 Mar 7.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Disease Models, Animal
  • Humans
  • Mice
  • Mice, Transgenic
  • Mutation*
  • Neoplasms / genetics*
  • Neoplasms / pathology