@article{19aaaebd9f144a0daa5e159669fbc277,
title = "A renal cell carcinoma tumorgraft platform to advance precision medicine",
abstract = "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.",
keywords = "BAP1, HIF, NGS, PET, PT2385, TAK-243, VHL, animal models, belzutifan, biomarkers, iPET, immunoPET, kidney cancer, metabolomics, molecular imaging, patient-derived xenograft, radiotracer, renal cell carcinoma",
author = "Roy Elias and Tcheuyap, {Vanina T.} and Kaushik, {Akash K.} and Nirmish Singla and Ming Gao and {Reig Torras}, Oscar and Alana Christie and Aditi Mulgaonkar and Layton Woolford and Christina Stevens and Kettimuthu, {Kavitha Priya} and Andrea Pavia-Jimenez and Boroughs, {Lindsey K.} and Allison Joyce and Marianna Dakanali and Hollis Notgrass and Vitaly Margulis and Cadeddu, {Jeffrey A.} and Ivan Pedrosa and Williams, {Noelle S.} and Xiankai Sun and DeBerardinis, {Ralph J.} and {\"O}z, {Orhan K.} and Hua Zhong and Somasekar Seshagiri and Zora Modrusan and Cantarel, {Brandi L.} and Payal Kapur and James Brugarolas",
note = "Funding Information: More than 900 individuals at UTSW and its affiliated county hospital donated their samples. We acknowledge the support and cooperation from Parkland Health and Hospital System staff for voluntarily participating in study data collection. The TG resource was supported by an American Cancer Society Research Scholar grant ( 115739 ) and National Institutes of Health grant P50CA196516 . Genomic studies were funded primarily by S.S. from Genentech / Roche . Metabolomic studies were funded through an NCI Outstanding Investigator Award ( R35CA22044901 to R.J.D.). We acknowledge the UTSW Tissue Resource and Small Animal Imaging Resource, which are supported in part by P30CA142543 ; the Cyclotron and Radiochemistry Program, supported in part by the Cancer Prevention and Research Institute of Texas (CPRIT; RP170638 and RP110771 ), and the institutionally supported Preclinical Pharmacology Core. R.E. is supported by the Burroughs Wellcome Fund , O.R.T. by the FSEOM/Fundaci{\'o}n Cris Contra el Cancer 2018 , O.K.O. by the Robert W. Parkey, M.D. Distinguished Professorship in Radiology , I.P. by R01CA154475 , N.S. by Ruth L. Kirschstein National Research Service Award T32 CA136515-09 and the Physician Scientist Training Program , B.L.C. by funds from CPRIT ( RP150596 ), P.K. through an endowment from the Jan and Bob Pickens Distinguished Professorship in Medical Science and Brock Fund for Medical Science Chair in Pathology , and J.B. by the Sherry Wigley Crow Cancer Research Endowment in Honor of Robert Lewis Kirby, MD . Funding Information: More than 900 individuals at UTSW and its affiliated county hospital donated their samples. We acknowledge the support and cooperation from Parkland Health and Hospital System staff for voluntarily participating in study data collection. The TG resource was supported by an American Cancer Society Research Scholar grant (115739) and National Institutes of Health grant P50CA196516. Genomic studies were funded primarily by S.S. from Genentech/Roche. Metabolomic studies were funded through an NCI Outstanding Investigator Award (R35CA22044901 to R.J.D.). We acknowledge the UTSW Tissue Resource and Small Animal Imaging Resource, which are supported in part by P30CA142543; the Cyclotron and Radiochemistry Program, supported in part by the Cancer Prevention and Research Institute of Texas (CPRIT; RP170638 and RP110771), and the institutionally supported Preclinical Pharmacology Core. R.E. is supported by the Burroughs Wellcome Fund, O.R.T. by the FSEOM/Fundaci?n Cris Contra el Cancer 2018, O.K.O. by the Robert W. Parkey, M.D. Distinguished Professorship in Radiology, I.P. by R01CA154475, N.S. by Ruth L. Kirschstein National Research Service Award T32 CA136515-09 and the Physician Scientist Training Program, B.L.C. by funds from CPRIT (RP150596), P.K. through an endowment from the Jan and Bob Pickens Distinguished Professorship in Medical Science and Brock Fund for Medical Science Chair in Pathology, and J.B. by the Sherry Wigley Crow Cancer Research Endowment in Honor of Robert Lewis Kirby, MD. Conceptualization, R.E. P.K. and J.B.; TG model acquisition, V.T.T. L.W. C.S. A.P.-J. A.J. H.N. P.K. and J.B.; genomic/transcriptomic analysis, R.E. O.R.T. H.Z. S.S. Z.M. B.L.C. and J.B.; metabolomics, L.K.B. A.K.K. and R.J.D.; immunoPET, A.M. M.D. X.S. O.K.?. I.P. and J.B.; pharmacokinetics, V.T.T. K.P.K. N.S.W. M.G. and J.B.; drug trials: V.T.T. M.G. and J.B.; data curation, R.E. V.T.T. A.K.K. N.S. A.C. A.M. L.W. C.S. A.P.-J. N.S.W. X.S. R.J.D. O.K.?. H.Z. S.S. Z.M. B.L.C. P.K. and J.B.; writing ? original draft: R.E. and N.S.; writing ? review & editing, V.T.T. A.K.K. C.S. I.P. N.S.W. X.S. R.J.D. O.K.?. H.Z. S.S. Z.M. B.L.C. P.K. and J.B.; visualization, R.E. A.C. and A.K.K.; resources, R.E. V.T.T. L.W. C.S. A.P.-J. A.J. V.M. J.A.C. I.P. N.S.W. X.S. R.J.D. O.K.?. H.Z. B.L.C. S.S. Z.M. P.K. and J.B.; supervision, I.P. N.S.W. X.S. R.J.D. O.K.?. H.Z. B.L.C. P.K. and J.B.; funding acquisition, J.B. 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 [18F]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. Publisher Copyright: {\textcopyright} 2021 The Authors",
year = "2021",
month = nov,
day = "23",
doi = "10.1016/j.celrep.2021.110055",
language = "English (US)",
volume = "37",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "8",
}