A renal cell carcinoma tumorgraft platform to advance precision medicine.
Autor: | Elias R; Kidney Cancer Program, Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, TX, USA; Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX, USA., Tcheuyap VT; Kidney Cancer Program, Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, TX, USA., Kaushik AK; Howard Hughes Medical Institute and Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA., Singla N; Kidney Cancer Program, Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, TX, USA; Department of Urology, The University of Texas Southwestern Medical Center, Dallas, TX, USA., Gao M; Kidney Cancer Program, Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, TX, USA., Reig Torras O; Kidney Cancer Program, Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, TX, USA., Christie A; Kidney Cancer Program, Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, TX, USA; Division of Biostatistics, Department of Clinical Sciences, The University of Texas Southwestern Medical Center, Dallas, TX, USA., Mulgaonkar A; Department of Radiology, The University of Texas Southwestern Medical Center, Dallas, TX, USA., Woolford L; Kidney Cancer Program, Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, TX, USA., Stevens C; Kidney Cancer Program, Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, TX, USA., Kettimuthu KP; Department of Biochemistry, The University of Texas Southwestern Medical Center, Dallas, TX, USA., Pavia-Jimenez A; Kidney Cancer Program, Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, TX, USA., Boroughs LK; Howard Hughes Medical Institute and Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA., Joyce A; Kidney Cancer Program, Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, TX, USA., Dakanali M; Department of Radiology, The University of Texas Southwestern Medical Center, Dallas, TX, USA., Notgrass H; Department of Pathology, The University of Texas Southwestern Medical Center, Dallas, TX, USA., Margulis V; Kidney Cancer Program, Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, TX, USA; Department of Urology, The University of Texas Southwestern Medical Center, Dallas, TX, USA., Cadeddu JA; Kidney Cancer Program, Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, TX, USA; Department of Urology, The University of Texas Southwestern Medical Center, Dallas, TX, USA., Pedrosa I; Kidney Cancer Program, Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, TX, USA; Department of Radiology, The University of Texas Southwestern Medical Center, Dallas, TX, USA; Advanced Imaging Research Center, The University of Texas Southwestern Medical Center, Dallas, TX, USA., Williams NS; Kidney Cancer Program, Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, TX, USA; Department of Bioinformatics, The University of Texas Southwestern Medical Center, Dallas, TX, USA., Sun X; Kidney Cancer Program, Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, TX, USA; Department of Radiology, The University of Texas Southwestern Medical Center, Dallas, TX, USA; Advanced Imaging Research Center, The University of Texas Southwestern Medical Center, Dallas, TX, USA., DeBerardinis RJ; Kidney Cancer Program, Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, TX, USA; Howard Hughes Medical Institute and Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA., Öz OK; Kidney Cancer Program, Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, TX, USA; Department of Radiology, The University of Texas Southwestern Medical Center, Dallas, TX, USA., Zhong H; Department of Pathology, The University of Texas Southwestern Medical Center, Dallas, TX, USA; Department of Bioinformatics, The University of Texas Southwestern Medical Center, Dallas, TX, USA., Seshagiri S; Department of Microchemistry, Proteomics, Lipidomics and NGS, Genentech, Inc., South San Francisco, CA, USA., Modrusan Z; Department of Microchemistry, Proteomics, Lipidomics and NGS, Genentech, Inc., South San Francisco, CA, USA., Cantarel BL; Department of Bioinformatics, The University of Texas Southwestern Medical Center, Dallas, TX, USA., Kapur P; Kidney Cancer Program, Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, TX, USA; Department of Urology, The University of Texas Southwestern Medical Center, Dallas, TX, USA; Department of Pathology, The University of Texas Southwestern Medical Center, Dallas, TX, USA., Brugarolas J; Kidney Cancer Program, Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, TX, USA; Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX, USA. Electronic address: james.brugarolas@utsw.edu. |
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Jazyk: | angličtina |
Zdroj: | Cell reports [Cell Rep] 2021 Nov 23; Vol. 37 (8), pp. 110055. |
DOI: | 10.1016/j.celrep.2021.110055 |
Abstrakt: | Renal cell carcinoma (RCC) encompasses a heterogenous group of tumors, but representative preclinical models are lacking. We previously showed that patient-derived tumorgraft (TG) models recapitulate the biology and treatment responsiveness. Through systematic orthotopic implantation of tumor samples from 926 ethnically diverse individuals into non-obese diabetic (NOD)/severe combined immunodeficiency (SCID) mice, we generate a resource comprising 172 independently derived, stably engrafted TG lines from 148 individuals. TG lines are characterized histologically and genomically (whole-exome [n = 97] and RNA [n = 102] sequencing). The platform features a variety of histological and oncogenotypes, including TCGA clades further corroborated through orthogonal metabolomic analyses. We illustrate how it enables a deeper understanding of RCC biology; enables the development of tissue- and imaging-based molecular probes; and supports advances in drug development. Competing Interests: Declaration of interests J.B. is an employee/paid consultant for Arrowhead, Calithera, Esai, Exelixis, and Johnson & Johnson and reports receiving commercial research grants from Arrowhead. J.B. and X.S. have a patent application on [(18)F]PT2385. I.P. reports personal fees from Bayer Healthcare and Health Tech International, personal fees for serving in an Advisory Committee for Merck, and others from Philips Healthcare, all outside of the submitted work. R.J.D. is a founder of Atavistik Bio and a member of the Scientific Advisory Boards of Agios Pharmaceuticals, Vida Ventures, and Nirogy Therapeutics. (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.) |
Databáze: | MEDLINE |
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