Establishing a human renal cell carcinoma tumorgraft platform for preclinical drug testing

作者: Andrea Pavía-Jiménez , Vanina Toffessi Tcheuyap , James Brugarolas

DOI: 10.1038/NPROT.2014.108

关键词: In vivoRegulation of gene expressionDrugCancer researchImmunologyGene expressionBiologyTransplantationHistologyRenal cell carcinomaCarcinoma

摘要: Traditionally, xenograft models have been used to study tumors in vivo. However, their utility is reduced by the use of tumor cell lines for implantation. Tumorgrafts (TGs; also known as patient-derived xenografts (PDXs)), which involve samples, are increasingly recognized more representative than traditional xenografts. Furthermore, we showed previously that renal carcinoma (RCC) TGs retain histology, gene expression, DNA copy number alterations, mutations and treatment responsiveness patient tumors. In skilled hands, implantations require ≤5 min per mouse, typically grow 1 cm 1-4 months. Here outline process implantation RCC samples into kidneys immunodeficient mice, well s.c. preclinical drug testing, including guidelines design execution trials. extensive applications besides therapeutic studies may identify biomarkers mechanisms resistance. addition, they provide insights biology.

参考文章(27)
Dustin M. Walters, James M. Lindberg, Sara J. Adair, Timothy E. Newhook, Catharine R. Cowan, Jayme B. Stokes, Cheryl A. Borgman, Edward B. Stelow, Bryce T. Lowrey, Maria E. Chopivsky, Tona M. Gilmer, John T. Parsons, Todd W. Bauer, Inhibition of the growth of patient-derived pancreatic cancer xenografts with the MEK inhibitor trametinib is augmented by combined treatment with the epidermal growth factor receptor/HER2 inhibitor lapatinib Neoplasia. ,vol. 15, pp. 143- 155 ,(2013) , 10.1593/NEO.121712
John M.L. Ebos, Christina R. Lee, William Cruz-Munoz, Georg A. Bjarnason, James G. Christensen, Robert S. Kerbel, Accelerated Metastasis after Short-Term Treatment with a Potent Inhibitor of Tumor Angiogenesis Cancer Cell. ,vol. 15, pp. 232- 239 ,(2009) , 10.1016/J.CCR.2009.01.021
Marco Gerlinger, Stuart Horswell, James Larkin, Andrew J Rowan, Max P Salm, Ignacio Varela, Rosalie Fisher, Nicholas McGranahan, Nicholas Matthews, Claudio R Santos, Pierre Martinez, Benjamin Phillimore, Sharmin Begum, Adam Rabinowitz, Bradley Spencer-Dene, Sakshi Gulati, Paul A Bates, Gordon Stamp, Lisa Pickering, Martin Gore, David L Nicol, Steven Hazell, P Andrew Futreal, Aengus Stewart, Charles Swanton, Genomic architecture and evolution of clear cell renal cell carcinomas defined by multiregion sequencing Nature Genetics. ,vol. 46, pp. 225- 233 ,(2014) , 10.1038/NG.2891
Patrick L. Garcia, Leona N. Council, John D. Christein, J. Pablo Arnoletti, Marty J. Heslin, Tracy L. Gamblin, Joseph H. Richardson, Mary-Ann Bjornsti, Karina J. Yoon, Development and Histopathological Characterization of Tumorgraft Models of Pancreatic Ductal Adenocarcinoma PLoS ONE. ,vol. 8, pp. e78183- ,(2013) , 10.1371/JOURNAL.PONE.0078183
Alberto Ocana, Atanasio Pandiella, Lillian L. Siu, Ian F. Tannock, Preclinical development of molecular-targeted agents for cancer Nature Reviews Clinical Oncology. ,vol. 8, pp. 200- 209 ,(2011) , 10.1038/NRCLINONC.2010.194
Christopher L Morton, Peter J Houghton, Establishment of human tumor xenografts in immunodeficient mice. Nature Protocols. ,vol. 2, pp. 247- 250 ,(2007) , 10.1038/NPROT.2007.25
K. Garber, From Human to Mouse and Back: “Tumorgraft” Models Surge in Popularity Journal of the National Cancer Institute. ,vol. 101, pp. 6- 8 ,(2009) , 10.1093/JNCI/DJN481
X. Y. Fu, J. M. Besterman, A. Monosov, R. M. Hoffman, Models of human metastatic colon cancer in nude mice orthotopically constructed by using histologically intact patient specimens. Proceedings of the National Academy of Sciences of the United States of America. ,vol. 88, pp. 9345- 9349 ,(1991) , 10.1073/PNAS.88.20.9345
Yoko S DeRose, Guoying Wang, Yi-Chun Lin, Philip S Bernard, Saundra S Buys, Mark T W Ebbert, Rachel Factor, Cindy Matsen, Brett A Milash, Edward Nelson, Leigh Neumayer, R Lor Randall, Inge J Stijleman, Bryan E Welm, Alana L Welm, Tumor grafts derived from women with breast cancer authentically reflect tumor pathology, growth, metastasis and disease outcomes Nature Medicine. ,vol. 17, pp. 1514- 1520 ,(2011) , 10.1038/NM.2454
B Rubio-Viqueira, M Hidalgo, Direct in vivo xenograft tumor model for predicting chemotherapeutic drug response in cancer patients. Clinical Pharmacology & Therapeutics. ,vol. 85, pp. 217- 221 ,(2009) , 10.1038/CLPT.2008.200