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Updated: Oct 12, 2025
Utilization of Ultrasound Guided Tissue-directed Cellular Implantation for the Establishment of Biologically Relevant Metastatic Tumor Xenografts
Published on: May 25, 2018
A renal cell carcinoma tumorgraft platform to advance precision medicine
Roy Elias1, Vanina T Tcheuyap2, Akash K Kaushik3
1Kidney 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.
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.
Insights
Researchers created new patient-derived tumor models for renal cell carcinoma (RCC) to better understand this complex cancer. These models will aid in developing new treatments and diagnostic tools for kidney cancer.
Area of Science:
- Oncology
- Translational Research
- Genomics
Background:
- Renal cell carcinoma (RCC) is a heterogeneous cancer with a lack of adequate preclinical models.
- Previous work demonstrated the utility of patient-derived tumorgraft (TG) models in recapitulating RCC biology and treatment response.
Purpose of the Study:
- To establish a comprehensive resource of patient-derived tumorgraft (TG) models for renal cell carcinoma (RCC).
- To characterize these models genomically and histologically to ensure biological fidelity.
- To facilitate deeper understanding of RCC biology and support advancements in drug development and molecular probe creation.
Main Methods:
- Systematic orthotopic implantation of tumor samples from 926 diverse individuals into NOD/SCID mice.
- Generation and characterization of 172 independently derived, stably engrafted TG lines.
- Histological, whole-exome sequencing (n=97), RNA sequencing (n=102), and metabolomic analyses were performed.
Main Results:
- A valuable resource of 172 RCC tumorgraft lines was successfully generated from 148 patients.
- The TG lines exhibit diverse histological subtypes and oncogenotypes, including representation of TCGA clades.
- Orthogonal metabolomic analyses corroborated genomic findings, confirming the biological relevance of the models.
Conclusions:
- The established TG platform provides a robust preclinical resource for studying renal cell carcinoma heterogeneity.
- These models are suitable for advancing the development of tissue- and imaging-based molecular probes.
- The resource will significantly support the development of novel therapeutic strategies for RCC.
