Lost in translation: animal models and clinical trials in cancer treatment.

Due to practical and ethical concerns associated with human experimentation, animal models have been essential in cancer research. However, the average rate of successful translation from animal models to clinical cancer trials is less than 8%. Animal models are limited in their ability to mimic the extremely complex process of human carcinogenesis, physiology and progression. Therefore the safety and efficacy identified in animal studies is generally not translated to human trials. Animal models can serve as an important source of in vivo information, but alternative translational approaches have emerged that may eventually replace the link between in vitro studies and clinical applications. This review summarizes the current state of animal model translation to clinical practice, and offers some explanations for the general lack of success in this process. In addition, some alternative strategies to the classic in vivo approach are discussed.

[1]  V. Apostolopoulos Cancer vaccines: looking to the future , 2013, Expert review of vaccines.

[2]  K. Nathanson,et al.  Immunotherapy at Large: The road to personalized cancer vaccines , 2013, Nature Medicine.

[3]  A. Aruga,et al.  Immunological monitoring of anticancer vaccines in clinical trials , 2013, Oncoimmunology.

[4]  David Beare,et al.  Frequent mutation of the major cartilage collagen gene COL2A1 in chondrosarcoma , 2013, Nature Genetics.

[5]  T. Miyakawa,et al.  Genomic responses in mouse models poorly mimic human inflammatory diseases , 2013 .

[6]  J. Olson,et al.  Hedgehog pathway inhibitor saridegib (IPI-926) increases lifespan in a mouse medulloblastoma model , 2012, Proceedings of the National Academy of Sciences.

[7]  Natalie Cook,et al.  Predictive in vivo animal models and translation to clinical trials. , 2012, Drug discovery today.

[8]  Heidi Ledford,et al.  Translational research: 4 ways to fix the clinical trial , 2011, Nature.

[9]  J. Arrowsmith Trial watch: Phase III and submission failures: 2007–2010 , 2011, Nature Reviews Drug Discovery.

[10]  Raouf Khalil,et al.  Faculty of 1000 evaluation for Matrix metalloproteinase inhibitors: a critical appraisal of design principles and proposed therapeutic utility. , 2010 .

[11]  H. Attarwala,et al.  TGN1412: From Discovery to Disaster , 2010, Journal of young pharmacists : JYP.

[12]  J. Bailar,et al.  Toxicity Testing in the 21st Century: A Vision and a Strategy , 2010, Journal of toxicology and environmental health. Part B, Critical reviews.

[13]  P. Ferdinandy,et al.  Matrix Metalloproteinase Inhibitors , 2010, Drugs.

[14]  D. Howells,et al.  Publication Bias in Reports of Animal Stroke Studies Leads to Major Overstatement of Efficacy , 2010, PLoS biology.

[15]  G. Curt,et al.  One in five cancer clinical trials is published: a terrible symptom--what's the diagnosis? , 2008, The oncologist.

[16]  R. Matthews,et al.  Medical progress depends on animal models - doesn't it? , 2008, Journal of the Royal Society of Medicine.

[17]  J. Schellens,et al.  The impact of FDA and EMEA guidelines on drug development in relation to Phase 0 trials , 2007, British Journal of Cancer.

[18]  P. Sandercock,et al.  Comparison of treatment effects between animal experiments and clinical trials: systematic review , 2006, BMJ : British Medical Journal.

[19]  Nicki Panoskaltsis,et al.  Cytokine storm in a phase 1 trial of the anti-CD28 monoclonal antibody TGN1412. , 2006, The New England journal of medicine.

[20]  C. Overall,et al.  Towards third generation matrix metalloproteinase inhibitors for cancer therapy , 2006, British Journal of Cancer.

[21]  JoAnn C L Schuh,et al.  Trials, Tribulations, and Trends in Tumor Modeling in Mice , 2004, Toxicologic pathology.

[22]  Elissa J Chesler,et al.  Identification and ranking of genetic and laboratory environment factors influencing a behavioral trait, thermal nociception, via computational analysis of a large data archive , 2002, Neuroscience & Biobehavioral Reviews.

[23]  Steven K. Gibb Toxicity testing in the 21st century: a vision and a strategy. , 2008, Reproductive toxicology.

[24]  B. Fingleton,et al.  Matrix metalloproteinases as valid clinical targets. , 2007, Current pharmaceutical design.

[25]  S. H. van der Burg,et al.  Vaccination for treatment and prevention of cancer in animal models. , 2006, Advances in immunology.

[26]  Luna,et al.  Translation of Research Evidence From Animals to Humans , 2006 .

[27]  Innovation OR Stagnation Challenge and Opportunity on the Critical Path to New Medical Products , 2004 .