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Review
. 2022 Apr 7:12:871252.
doi: 10.3389/fonc.2022.871252. eCollection 2022.

Models of Renal Cell Carcinoma Used to Investigate Molecular Mechanisms and Develop New Therapeutics

Daniel D Shapiro  1   2 , Maria Virumbrales-Muñoz  3   4 , David J Beebe  3   5 , E Jason Abel  1
Affiliations
Review

Models of Renal Cell Carcinoma Used to Investigate Molecular Mechanisms and Develop New Therapeutics

Daniel D Shapiro et al. Front Oncol. .

Abstract

Modeling renal cell carcinoma is critical to investigating tumor biology and therapeutic mechanisms. Multiple systems have been developed to represent critical components of the tumor and its surrounding microenvironment. Prominent in vitro models include traditional cell cultures, 3D organoid models, and microphysiological devices. In vivo models consist of murine patient derived xenografts or genetically engineered mice. Each system has unique advantages as well as limitations and researchers must thoroughly understand each model to properly investigate research questions. This review addresses common model systems for renal cell carcinoma and critically evaluates their performance and ability to measure tumor characteristics.

Keywords: cell culture; microfluidics; organoid; preclinical models; renal cell carcinoma; xenograft.

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Conflict of interest statement

DB holds equity in Bellbrook Labs LLC, Tasso Inc., Turba LLC, Salus Discovery LLC, Stacks to the Future LLC, Lynx Biosciences Inc., Flambeau Diagnostics, and Onexio Biosystems. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Renal cell carcinoma genetic evolution. This model of renal cell carcinoma evolution demonstrates chromosome 3p loss as the initial “first-hit” event. Subsequent biallelic loss of VHL occurs as a second hit. Tumor cells then may undergo multiple different pathways or “branches” of evolution based on mutations in other driver genes such as SETD2, PBRM1, and BAP1. These distinct evolutionary branches create different tumor phenotypes (31).
Figure 2
Figure 2
Microfluidic model systems used for renal cell carcinoma research. (A) Schematic of the RCC tumor microenvironment. (B) Microfluidic model of RCC response using primary normal and tumor-associated endothelial vessels. (C) Microfluidic model of RCC angiogenesis using primary epithelial-derived spheroids and Human Umbilical Cord Endothelial cell vessel models. (D) Microfluidic of RCC development and angiogenesis using RCC cell lines or primary epithelial cells and iPSC-derived endothelial cell vessels.
Figure 3
Figure 3
Species specific differences in the chromosomal locations of renal cell carcinoma driver genes.
Figure 4
Figure 4
Model systems used for renal cell carcinoma research. TME, tumor microenvironment; RCC, renal cell carcinoma.
See this image and copyright information in PMC

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