Open Access Open Access  Restricted Access Subscription or Fee Access

Genetically Engineered Mouse Models in Cancer Drug Development

Rutuja Sanjay Deshmukh

Abstract


Higher rate of compounds entering clinical testing as effective anticancer drugs indicates necessity for better methods for preclinical studies. Therapeutic activity of compounds tested in xenograft mouse model and their efficacy in humans shows poor correlation, but it does not mean that genetically engineered mouse model will be of controlled use in drug development. Use of genetically engineered mouse model is one of the best solutions for human cancer. It facilitates the identification of the right target, right drug and the right patients. The use of tumor bearing genetically engineered mouse improves preclinical testing. These models summed up specific molecular pathways in tumor initiation and propagation. These also provides a biological system to study the disease process for generating new therapies and testing molecularly targeted drugs. In this review, we discuss the advantages and limitations of genetically engineered mice and better solutions for adapting these tumors for use in preclinical testing. In this article, we discuss uses of xenograft mouse models for cancer drug development, then describe the opportunities and challenges in the application of novel genetically engineered mouse models that mimics the genetic and biological evolution of human cancer. There are several applications in target validation, evaluation of tumor response, investigation of pharmacodynamics markers of drug action and understanding toxicity has the ability to markedly improve the success of cancer drug development. 

Keywords


genetic engineering, mouse model, cancer, drug development

Full Text:

PDF

References


Society for Clinical Trials Board of Directors, The Society for Clinical Trials opposes US legislation to permit marketing of unproven medical therapies for seriously ill patients, Clin. Trials 3 (2006) 154–157.

M. Suggitt, M.C. Bibby, 50 years of preclinical anticancer drug screening: empirical to target-driven approaches, Clin. Cancer Res. 11 (2005) 971–981.

E.A. Sausville, A.M. Burger, Contributions of human tumor xenografts to anticancer drug development, Cancer Res. 66 (2006) 3351–3354.

T. Van Dyke, T. Jacks, Cancer modeling in the modern era: progress and challenges, Cell. 108 (2002) 135–144.

A. Leder, P.K. Pattengale, A. Kuo, T.A. Stewart, P. Leder, Con- sequences of widespread deregulation of the c-myc gene in transgenic mice: multiple neoplasms and normal development, Cell 45 (1986) 485–495

C.T. Guy, R.D. Cardiff, W.J. Muller, Induction of mammary tumors by expression of polyomavirus middle T oncogene: a transgenic mouse model for metastatic disease, Mol. Cell. Biol. 12 (1992) 954–961.

J.E. Maglione, E.T. McGoldrick, L.J. Young, R. Namba, J.P. Gregg, L. Liu, D. Moghanaki, L.G. Ellies, A.D. Borowsky, R.D. Cardiff, C.L. MacLeod, Polyomavirus middle T-induced mammary intra epithelial neoplasia outgrowths: single origin, divergent evolution, and multiple outcomes, Mol. Cancer Ther. 3 (2004) 941–953.

H.H. Fiebig, A.M. Burger, Human tumor xenografts and explants, in: B.A. Teicher (Ed.), Tumor Models in Cancer Research, Humana Press Inc., 2002, pp. 113–137.

S. Huang, Y. Li, Y. Chen, K. Podsypanina, M. Chamorro, A.B. Olshen, K.V. Desai, A. Tann, D. Petersen, J.E. Green, H.E. Varmus, Changes in gene expression during the development of mammary tumors in MMTV-Wnt-1 transgenic mice, Genome Biol. 6 (2005) R84.


Refbacks

  • There are currently no refbacks.