TY - JOUR
T1 - Establishing a human renal cell carcinoma tumorgraft platform for preclinical drug testing
AU - Pavía-Jiménez, Andrea
AU - Tcheuyap, Vanina Toffessi
AU - Brugarolas, James
N1 - Funding Information:
acknowleDGMents We are thankful to S. Sivanand for her help in establishing the program, P. Kapur for providing RCC histology pictures, and S. Cohn, R. McKay, S. Peña-Llopis, T. Anh Tran and S. Vega-Rubín-de-Celis for reviewing the manuscript. The work described herein was supported by grants from the American Cancer Society (RSG115739), the V Foundation, the US National Institutes of Health (R01CA175754), and the Cancer Prevention and Research Institute of Texas (RP101075, RP130172 and RP130603) to J.B., as well as a Cancer Center Core grant (P30CA142543). J.B. is a Virginia Murchison Linthicum Endowed Scholar in Medical Research.
PY - 2014/8
Y1 - 2014/8
N2 - 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 patient-derived tumor samples, are increasingly recognized as more representative models than traditional xenografts. Furthermore, we showed previously that renal cell carcinoma (RCC) TGs retain the histology, gene expression, DNA copy number alterations, mutations and treatment responsiveness of patient tumors. In skilled hands, implantations require ' ‰' 5 min per mouse, and TGs typically grow to 1 cm in 1-4 months. Here we outline the process of implantation of patient-derived RCC samples into the kidneys of immunodeficient mice, as well as the s.c. implantation for preclinical drug testing, including guidelines for the design and execution of drug trials. TGs have extensive applications besides therapeutic studies and may identify biomarkers and mechanisms of resistance. In addition, they may provide insights into tumor biology.
AB - 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 patient-derived tumor samples, are increasingly recognized as more representative models than traditional xenografts. Furthermore, we showed previously that renal cell carcinoma (RCC) TGs retain the histology, gene expression, DNA copy number alterations, mutations and treatment responsiveness of patient tumors. In skilled hands, implantations require ' ‰' 5 min per mouse, and TGs typically grow to 1 cm in 1-4 months. Here we outline the process of implantation of patient-derived RCC samples into the kidneys of immunodeficient mice, as well as the s.c. implantation for preclinical drug testing, including guidelines for the design and execution of drug trials. TGs have extensive applications besides therapeutic studies and may identify biomarkers and mechanisms of resistance. In addition, they may provide insights into tumor biology.
UR - http://www.scopus.com/inward/record.url?scp=84905014283&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84905014283&partnerID=8YFLogxK
U2 - 10.1038/nprot.2014.108
DO - 10.1038/nprot.2014.108
M3 - Article
C2 - 25010905
AN - SCOPUS:84905014283
SN - 1754-2189
VL - 9
SP - 1848
EP - 1859
JO - Nature Protocols
JF - Nature Protocols
IS - 8
ER -