A renal cell carcinoma tumorgraft platform to advance precision medicine

Cell Rep. 2021 Nov 23;37(8):110055. doi: 10.1016/j.celrep.2021.110055.

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.