Mouse tumour models to guide drug development and identify resistance mechanisms

J Pathol. 2014 Jan;232(2):103-11. doi: 10.1002/path.4285.

Abstract

We need improved, translatable and predictive tumour models for the evaluation of response and the evolution of resistance to targeted therapeutics. We provide a review of the use of different types of preclinical tumour models to evaluate novel anticancer agents, and model the rapidly evolving landscape of resistance to targeted therapy. We focus on describing the various preclinical models available for candidate drug development and design considerations for preclinical experiments, depending on the aspect of drug action being interrogated. We discuss selected examples of how experimental findings have translated into clinical outcomes for targeted agents, predicted mechanisms that drive resistance and strategies to overcome the evolution thereof. We discuss challenges in preclinical experimental design and interpretation and possible improvements in animal models of therapeutic response and resistance, with an emphasis on improved translation of experimental research into clinical practice.

Keywords: GEMM; PDX; cancer; mouse model; resistance; targeted therapy; xenograft.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Biomarkers, Tumor / metabolism
  • Drug Discovery / methods*
  • Drug Resistance, Neoplasm*
  • Humans
  • Mice
  • Molecular Targeted Therapy
  • Neoplasms, Experimental / drug therapy*
  • Neoplasms, Experimental / metabolism
  • Neoplasms, Experimental / pathology
  • Signal Transduction / drug effects
  • Translational Medical Research
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor