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Mouse tumour models to guide drug development and identify resistance mechanisms
Author(s) -
Das Thakur Meghna,
Pryer Nancy K,
Singh Mallika
Publication year - 2014
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.4285
Subject(s) - drug resistance , drug development , preclinical research , acquired resistance , medicine , resistance (ecology) , translation (biology) , drug , computer science , computational biology , bioinformatics , pharmacology , biology , medical physics , ecology , biochemistry , messenger rna , gene , microbiology and biotechnology
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. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.