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Open AccessEditorial

Patient-Derived Xenograft Models in Cancer Research

by Wytske M. van Weerden

Cancers 2021, 13(4), 815; https://doi.org/10.3390/cancers13040815 - 16 Feb 2021

Cited by 4 | Viewed by 1880

Abstract

This series of 12 articles, consisting of 9 original articles and 3 reviews, is presented by international leaders in translational cancer research [...] Full article

(This article belongs to the Special Issue Patient-Derived Xenograft-Models in Cancer Research)

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19 pages, 5217 KiB

Open AccessArticle

Implementing Systems Modelling and Molecular Imaging to Predict the Efficacy of BCL-2 Inhibition in Colorectal Cancer Patient-Derived Xenograft Models

by Alice C. O’Farrell, Monika A. Jarzabek, Andreas U. Lindner, Steven Carberry, Emer Conroy, Ian S. Miller, Kate Connor, Liam Shiels, Eugenia R. Zanella, Federico Lucantoni, Adam Lafferty, Kieron White, Mariangela Meyer Villamandos, Patrick Dicker, William M. Gallagher, Simon A. Keek, Sebastian Sanduleanu, Philippe Lambin, Henry C. Woodruff, Andrea Bertotti, Livio Trusolino, Annette T. Byrne and Jochen H. M. Prehn Show full author list Hide full author list

Cancers 2020, 12(10), 2978; https://doi.org/10.3390/cancers12102978 - 14 Oct 2020

Cited by 10 | Viewed by 3850

Abstract

Resistance to chemotherapy often results from dysfunctional apoptosis, however multiple proteins with overlapping functions regulate this pathway. We sought to determine whether an extensively validated, deterministic apoptosis systems model, ‘DR_MOMP’, could be used as a stratification tool for the apoptosis sensitiser and BCL-2 [...] Read more.

Resistance to chemotherapy often results from dysfunctional apoptosis, however multiple proteins with overlapping functions regulate this pathway. We sought to determine whether an extensively validated, deterministic apoptosis systems model, ‘DR_MOMP’, could be used as a stratification tool for the apoptosis sensitiser and BCL-2 antagonist, ABT-199 in patient-derived xenograft (PDX) models of colorectal cancer (CRC). Through quantitative profiling of BCL-2 family proteins, we identified two PDX models which were predicted by DR_MOMP to be sufficiently sensitive to 5-fluorouracil (5-FU)-based chemotherapy (CRC0344), or less responsive to chemotherapy but sensitised by ABT-199 (CRC0076). Treatment with ABT-199 significantly improved responses of CRC0076 PDXs to 5-FU-based chemotherapy, but showed no sensitisation in CRC0344 PDXs, as predicted from systems modelling. ¹⁸F-Fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG-PET/CT) scans were performed to investigate possible early biomarkers of response. In CRC0076, a significant post-treatment decrease in mean standard uptake value was indeed evident only in the combination treatment group. Radiomic CT feature analysis of pre-treatment images in CRC0076 and CRC0344 PDXs identified features which could phenotypically discriminate between models, but were not predictive of treatment responses. Collectively our data indicate that systems modelling may identify metastatic (m)CRC patients benefitting from ABT-199, and that ¹⁸F-FDG-PET could independently support such predictions. Full article

(This article belongs to the Special Issue Patient-Derived Xenograft-Models in Cancer Research)

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13 pages, 2303 KiB

Open AccessArticle

Fast, In Vivo Model for Drug-Response Prediction in Patients with B-Cell Precursor Acute Lymphoblastic Leukemia

by Anton Gauert, Nadine Olk, Helia Pimentel-Gutiérrez, Kathy Astrahantseff, Lasse D. Jensen, Yihai Cao, Angelika Eggert, Cornelia Eckert and Anja I.H. Hagemann

Cancers 2020, 12(7), 1883; https://doi.org/10.3390/cancers12071883 - 13 Jul 2020

Cited by 16 | Viewed by 4270

Abstract

Only half of patients with relapsed B-cell precursor (BCP) acute lymphoblastic leukemia (ALL) currently survive with standard treatment protocols. Predicting individual patient responses to defined drugs prior to application would help therapy stratification and could improve survival. With the purpose to aid personalized [...] Read more.

Only half of patients with relapsed B-cell precursor (BCP) acute lymphoblastic leukemia (ALL) currently survive with standard treatment protocols. Predicting individual patient responses to defined drugs prior to application would help therapy stratification and could improve survival. With the purpose to aid personalized targeted treatment approaches, we developed a human–zebrafish xenograft (ALL-ZeFiX) assay to predict drug response in a patient in 5 days. Leukemia blast cells were pericardially engrafted into transiently immunosuppressed Danio rerio embryos, and engrafted embryos treated for the test case, venetoclax, before single-cell dissolution for quantitative whole blast cell analysis. Bone marrow blasts from patients with newly diagnosed or relapsed BCP-ALL were successfully expanded in 60% of transplants in immunosuppressed zebrafish embryos. The response of BCP-ALL cell lines to venetoclax in ALL-ZeFiX assays mirrored responses in 2D cultures. Venetoclax produced varied responses in patient-derived BCP-ALL grafts, including two results mirroring treatment responses in two refractory BCP-ALL patients treated with venetoclax. Here we demonstrate proof-of-concept for our 5-day ALL-ZeFiX assay with primary patient blasts and the test case, venetoclax, which after expanded testing for further targeted drugs could support personalized treatment decisions within the clinical time window for decision-making. Full article

(This article belongs to the Special Issue Patient-Derived Xenograft-Models in Cancer Research)

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19 pages, 19990 KiB

Open AccessArticle

Applying Tissue Slice Culture in Cancer Research—Insights from Preclinical Proton Radiotherapy

by Theresa Suckert, Treewut Rassamegevanon, Johannes Müller, Antje Dietrich, Antonia Graja, Michael Reiche, Steffen Löck, Mechthild Krause, Elke Beyreuther and Cläre von Neubeck

Cancers 2020, 12(6), 1589; https://doi.org/10.3390/cancers12061589 - 16 Jun 2020

Cited by 16 | Viewed by 5403

Abstract

A challenge in cancer research is the definition of reproducible, reliable, and practical models, which reflect the effects of complex treatment modalities and the heterogeneous response of patients. Proton beam radiotherapy (PBRT), relative to conventional photon-based radiotherapy, offers the potential for iso-effective tumor [...] Read more.

A challenge in cancer research is the definition of reproducible, reliable, and practical models, which reflect the effects of complex treatment modalities and the heterogeneous response of patients. Proton beam radiotherapy (PBRT), relative to conventional photon-based radiotherapy, offers the potential for iso-effective tumor control, while protecting the normal tissue surrounding the tumor. However, the effects of PBRT on the tumor microenvironment and the interplay with newly developed chemo- and immunotherapeutic approaches are still open for investigation. This work evaluated thin-cut tumor slice cultures (TSC) of head and neck cancer and organotypic brain slice cultures (OBSC) of adult mice brain, regarding their relevance for translational radiooncology research. TSC and OBSC were treated with PBRT and investigated for cell survival with a lactate dehydrogenase (LDH) assay, DNA repair via the DNA double strand break marker γH2AX, as well as histology with regards to morphology. Adult OBSC failed to be an appropriate model for radiobiological research questions. However, histological analysis of TSC showed DNA damage and tumor morphological results, comparable to known in vivo and in vitro data, making them a promising model to study novel treatment approaches in patient-derived xenografts or primary tumor material. Full article

(This article belongs to the Special Issue Patient-Derived Xenograft-Models in Cancer Research)

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16 pages, 3969 KiB

Open AccessArticle

Impact of the Injection Site on Growth Characteristics, Phenotype and Sensitivity towards Cytarabine of Twenty Acute Leukaemia Patient-Derived Xenograft Models

by Julia Schueler, Gabriele Greve, Dorothée Lenhard, Milena Pantic, Anna Edinger, Eva Oswald and Michael Lübbert

Cancers 2020, 12(5), 1349; https://doi.org/10.3390/cancers12051349 - 25 May 2020

Cited by 5 | Viewed by 3860

Abstract

Rodent models have contributed significantly to the understanding of haematological malignancies. One important model system in this context are patient-derived xenografts (PDX). In the current study, we examined 20 acute leukaemia PDX models for growth behaviour, infiltration in haemopoietic organs and sensitivity towards [...] Read more.

Rodent models have contributed significantly to the understanding of haematological malignancies. One important model system in this context are patient-derived xenografts (PDX). In the current study, we examined 20 acute leukaemia PDX models for growth behaviour, infiltration in haemopoietic organs and sensitivity towards cytarabine. PDX were injected intratibially (i.t.), intrasplenicaly (i.s.) or subcutaneously (s.c.) into immune compromised mice. For 18/20 models the engraftment capacity was independent of the implantation site. Two models could exclusively be propagated in one or two specific settings. The implantation site did influence tumour growth kinetics as median overall survival differed within one model depending on the injection route. The infiltration pattern was similar in i.t. and i.s. models. In contrast to the s.c. implantation, only one model displayed circulating leukaemic cells outside of the locally growing tumour mass. Cytarabine was active in all four tested models. Nevertheless, the degree of sensitivity was specific for an individual model and implantation site. In summary, all three application routes turned out to be feasible for the propagation of PDX. Nevertheless, the distinct differences between the settings highlight the need for well characterized platforms to ensure the meaningful interpretation of data generated using those powerful tools. Full article

(This article belongs to the Special Issue Patient-Derived Xenograft-Models in Cancer Research)

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20 pages, 3236 KiB

Open AccessArticle

Multi-Modal PET and MR Imaging in the Hen’s Egg Test-Chorioallantoic Membrane (HET-CAM) Model for Initial In Vivo Testing of Target-Specific Radioligands

by Gordon Winter, Andrea B. F. Koch, Jessica Löffler, Mika Lindén, Christoph Solbach, Alireza Abaei, Hao Li, Gerhard Glatting, Ambros J. Beer and Volker Rasche

Cancers 2020, 12(5), 1248; https://doi.org/10.3390/cancers12051248 - 15 May 2020

Cited by 19 | Viewed by 4672

Abstract

The validation of novel target-specific radioligands requires animal experiments mostly using mice with xenografts. A pre-selection based on a simpler in vivo model would allow to reduce the number of animal experiments, in accordance with the 3Rs principles (reduction, replacement, refinement). In this [...] Read more.

The validation of novel target-specific radioligands requires animal experiments mostly using mice with xenografts. A pre-selection based on a simpler in vivo model would allow to reduce the number of animal experiments, in accordance with the 3Rs principles (reduction, replacement, refinement). In this respect, the chick embryo or hen’s egg test–chorioallantoic membrane (HET-CAM) model is of special interest, as it is not considered an animal until day 17. Thus, we evaluated the feasibility of quantitative analysis of target-specific radiotracer accumulation in xenografts using the HET-CAM model and combined positron emission tomography (PET) and magnetic resonance imaging (MRI). For proof-of-principle we used established prostate-specific membrane antigen (PSMA)-positive and PSMA-negative prostate cancer xenografts and the clinically widely used PSMA-specific PET-tracer [⁶⁸Ga]Ga-PSMA-11. Tracer accumulation was quantified by PET and tumor volumes measured with MRI (n = 42). Moreover, gamma-counter analysis of radiotracer accumulation was done ex-vivo. A three- to five-fold higher ligand accumulation in the PSMA-positive tumors compared to the PSMA-negative tumors was demonstrated. This proof-of-principle study shows the general feasibility of the HET-CAM xenograft model for target-specific imaging with PET and MRI. The ultimate value for characterization of novel target-specific radioligands now has to be validated in comparison to mouse xenograft experiments. Full article

(This article belongs to the Special Issue Patient-Derived Xenograft-Models in Cancer Research)

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19 pages, 5134 KiB

Open AccessArticle

Establishment and Characterization of Humanized Mouse NPC-PDX Model for Testing Immunotherapy

by Wai Nam Liu, Shin Yie Fong, Wilson Wei Sheng Tan, Sue Yee Tan, Min Liu, Jia Ying Cheng, Sherlly Lim, Lisda Suteja, Edwin Kunxiang Huang, Jerry Kok Yen Chan, Narayanan Gopalakrishna Iyer, Joe Poh Sheng Yeong, Darren Wan-Teck Lim and Qingfeng Chen

Cancers 2020, 12(4), 1025; https://doi.org/10.3390/cancers12041025 - 22 Apr 2020

Cited by 32 | Viewed by 7493

Abstract

Immune checkpoint blockade (ICB) monotherapy shows early promise for the treatment of nasopharyngeal carcinoma (NPC) in patients. Nevertheless, limited representative NPC models hamper preclinical studies to evaluate the efficacy of novel ICB and combination regimens. In the present study, we engrafted NPC biopsies [...] Read more.

Immune checkpoint blockade (ICB) monotherapy shows early promise for the treatment of nasopharyngeal carcinoma (NPC) in patients. Nevertheless, limited representative NPC models hamper preclinical studies to evaluate the efficacy of novel ICB and combination regimens. In the present study, we engrafted NPC biopsies in non-obese diabetic-severe combined immunodeficiency interleukin-2 receptor gamma chain-null (NSG) mice and established humanized mouse NPC-patient-derived xenograft (NPC-PDX) model successfully. Epstein–Barr virus was detected in the NPC in both NSG and humanized mice as revealed by Epstein–Barr virus-encoded small RNA (EBER) in situ hybridization (ISH) and immunohistochemical (IHC) staining. In the NPC-bearing humanized mice, the percentage of tumor-infiltrating CD8⁺ cytotoxic T cells was lowered, and the T cells expressed higher levels of various inhibitory receptors, such as programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) than those in blood. The mice were then treated with nivolumab and ipilimumab, and the anti-tumor efficacy of combination immunotherapy was examined. In line with paired clinical data, the NPC-PDX did not respond to the treatment in terms of tumor burden, whilst an immunomodulatory response was elicited in the humanized mice. From our results, human proinflammatory cytokines, such as interferon-gamma (IFN-γ) and interleukin-6 (IL-6) were significantly upregulated in plasma. After treatment, there was a decrease in CD4/CD8 ratio in the NPC-PDX, which also simulated the modulation of intratumoral CD4/CD8 profile from the corresponding donor. In addition, tumor-infiltrating T cells were re-activated and secreted more IFN-γ towards ex vivo stimulation, suggesting that other factors, including soluble mediators and metabolic milieu in tumor microenvironment may counteract the effect of ICB treatment and contribute to the tumor progression in the mice. Taken together, we have established and characterized a novel humanized mouse NPC-PDX model, which plausibly serves as a robust platform to test for the efficacy of immunotherapy and may predict clinical outcomes in NPC patients. Full article

(This article belongs to the Special Issue Patient-Derived Xenograft-Models in Cancer Research)

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20 pages, 8580 KiB

Open AccessFeature PaperArticle

Establishment and Characterisation of Heterotopic Patient-Derived Xenografts for Glioblastoma

by Sarah Meneceur, Annett Linge, Matthias Meinhardt, Sandra Hering, Steffen Löck, Rebecca Bütof, Dietmar Krex, Gabriele Schackert, Achim Temme, Michael Baumann, Mechthild Krause and Cläre von Neubeck

Cancers 2020, 12(4), 871; https://doi.org/10.3390/cancers12040871 - 3 Apr 2020

Cited by 6 | Viewed by 3555

Abstract

Glioblastoma is an aggressive brain tumour with a patient median survival of approximately 14 months. The development of innovative treatment strategies to increase the life span and quality of life of patients is hence essential. This requires the use of appropriate glioblastoma models [...] Read more.

Glioblastoma is an aggressive brain tumour with a patient median survival of approximately 14 months. The development of innovative treatment strategies to increase the life span and quality of life of patients is hence essential. This requires the use of appropriate glioblastoma models for preclinical testing, which faithfully reflect human cancers. The aim of this study was to establish glioblastoma patient-derived xenografts (PDXs) by heterotopic transplantation of tumour pieces in the axillae of NMRI nude mice. Ten out of 22 patients’ samples gave rise to tumours in mice. Their human origin was confirmed by microsatellite analyses, though minor changes were observed. The glioblastoma nature of the PDXs was corroborated by pathological evaluation. Latency times spanned from 48.5 to 370.5 days in the first generation. Growth curve analyses revealed an increase in the growth rate with increasing passages. The methylation status of the MGMT promoter in the primary material was maintained in the PDXs. However, a trend towards a more methylated pattern could be found. A correlation was observed between the take in mice and the proportion of Sox2⁺ cells (r = 0.49, p = 0.016) and nestin⁺ cells (r = 0.55, p = 0.007). Our results show that many PDXs maintain key features of the patients’ samples they derive from. They could thus be used as preclinical models to test new therapies and biomarkers. Full article

(This article belongs to the Special Issue Patient-Derived Xenograft-Models in Cancer Research)

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16 pages, 4385 KiB

Open AccessArticle

A Model of a Zebrafish Avatar for Co-Clinical Trials

by Alice Usai, Gregorio Di Franco, Patrizia Colucci, Luca Emanuele Pollina, Enrico Vasile, Niccola Funel, Matteo Palmeri, Luciana Dente, Alfredo Falcone, Luca Morelli and Vittoria Raffa

Cancers 2020, 12(3), 677; https://doi.org/10.3390/cancers12030677 - 13 Mar 2020

Cited by 41 | Viewed by 5061

Abstract

Animal “avatars” and co-clinical trials are being developed for possible use in personalized medicine in oncology. In a co-clinical trial, the cancer cells of the patient’s tumor are xenotransplanted into the animal avatar for drug efficacy studies, and the data collected in the [...] Read more.

Animal “avatars” and co-clinical trials are being developed for possible use in personalized medicine in oncology. In a co-clinical trial, the cancer cells of the patient’s tumor are xenotransplanted into the animal avatar for drug efficacy studies, and the data collected in the animal trial are used to plan the best drug treatment in the patient trial. Zebrafish have recently been proposed for implementing avatar models, however the lack of a general criterion for the chemotherapy dose conversion from humans to fish is a limitation in terms of conducting co-clinical trials. Here, we validate a simple, reliant and cost-effective avatar model based on the use of zebrafish embryos. By crossing data from safety and efficacy studies, we found a basic formula for estimating the equivalent dose for use in co-clinical trials which we validated in a clinical study enrolling 24 adult patients with solid cancers (XenoZ, NCT03668418). Full article

(This article belongs to the Special Issue Patient-Derived Xenograft-Models in Cancer Research)

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16 pages, 3115 KiB

Open AccessArticle

Novel Breast Cancer Brain Metastasis Patient-Derived Orthotopic Xenograft Model for Preclinical Studies

by Masanori Oshi, Maiko Okano, Aparna Maiti, Omar M. Rashid, Katsuharu Saito, Koji Kono, Ryusei Matsuyama, Itaru Endo and Kazuaki Takabe

Cancers 2020, 12(2), 444; https://doi.org/10.3390/cancers12020444 - 14 Feb 2020

Cited by 22 | Viewed by 4497

Abstract

The vast majority of mortality in breast cancer results from distant metastasis. Brain metastases occur in as many as 30% of patients with advanced breast cancer, and the 1-year survival rate of these patients is around 20%. Pre-clinical animal models that reliably reflect [...] Read more.

The vast majority of mortality in breast cancer results from distant metastasis. Brain metastases occur in as many as 30% of patients with advanced breast cancer, and the 1-year survival rate of these patients is around 20%. Pre-clinical animal models that reliably reflect the biology of breast cancer brain metastasis are needed to develop and test new treatments for this deadly condition. The patient-derived xenograft (PDX) model maintains many features of a donor tumor, such as intra-tumor heterogeneity, and permits the testing of individualized treatments. However, the establishment of orthotopic PDXs of brain metastasis is procedurally difficult. We have developed a method for generating such PDXs with high tumor engraftment and growth rates. Here, we describe this method and identify variables that affect its outcomes. We also compare the brain-orthotopic PDXs with ectopic PDXs grown in mammary pads of mice, and show that the responsiveness of PDXs to chemotherapeutic reagents can be dramatically affected by the site that they are in. Full article

(This article belongs to the Special Issue Patient-Derived Xenograft-Models in Cancer Research)

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Review

Jump to: Editorial, Research

20 pages, 301 KiB

Open AccessReview

Patient-Derived Xenograft and Organoid Models for Precision Medicine Targeting of the Tumour Microenvironment in Head and Neck Cancer

by Tet Woo Lee, Amy Lai, Julia K. Harms, Dean C. Singleton, Benjamin D. Dickson, Andrew M. J. Macann, Michael P. Hay and Stephen M. F. Jamieson

Cancers 2020, 12(12), 3743; https://doi.org/10.3390/cancers12123743 - 12 Dec 2020

Cited by 19 | Viewed by 3937

Abstract

Patient survival from head and neck squamous cell carcinoma (HNSCC), the seventh most common cause of cancer, has not markedly improved in recent years despite the approval of targeted therapies and immunotherapy agents. Precision medicine approaches that seek to individualise therapy through the [...] Read more.

Patient survival from head and neck squamous cell carcinoma (HNSCC), the seventh most common cause of cancer, has not markedly improved in recent years despite the approval of targeted therapies and immunotherapy agents. Precision medicine approaches that seek to individualise therapy through the use of predictive biomarkers and stratification strategies offer opportunities to improve therapeutic success in HNSCC. To enable precision medicine of HNSCC, an understanding of the microenvironment that influences tumour growth and response to therapy is required alongside research tools that recapitulate the features of human tumours. In this review, we highlight the importance of the tumour microenvironment in HNSCC, with a focus on tumour hypoxia, and discuss the fidelity of patient-derived xenograft and organoids for modelling human HNSCC and response to therapy. We describe the benefits of patient-derived models over alternative preclinical models and their limitations in clinical relevance and how these impact their utility in precision medicine in HNSCC for the discovery of new therapeutic agents, as well as predictive biomarkers to identify patients’ most likely to respond to therapy. Full article

(This article belongs to the Special Issue Patient-Derived Xenograft-Models in Cancer Research)

21 pages, 637 KiB

Open AccessReview

Patient-Derived Xenograft Models of Pancreatic Cancer: Overview and Comparison with Other Types of Models

by Patrick L. Garcia, Aubrey L. Miller and Karina J. Yoon

Cancers 2020, 12(5), 1327; https://doi.org/10.3390/cancers12051327 - 22 May 2020

Cited by 42 | Viewed by 6592

Abstract

Pancreatic cancer (PC) is anticipated to be second only to lung cancer as the leading cause of cancer-related deaths in the United States by 2030. Surgery remains the only potentially curative treatment for patients with pancreatic ductal adenocarcinoma (PDAC), the most common form [...] Read more.

Pancreatic cancer (PC) is anticipated to be second only to lung cancer as the leading cause of cancer-related deaths in the United States by 2030. Surgery remains the only potentially curative treatment for patients with pancreatic ductal adenocarcinoma (PDAC), the most common form of PC. Multiple recent preclinical studies focus on identifying effective treatments for PDAC, but the models available for these studies often fail to reproduce the heterogeneity of this tumor type. Data generated with such models are of unknown clinical relevance. Patient-derived xenograft (PDX) models offer several advantages over human cell line-based in vitro and in vivo models and models of non-human origin. PDX models retain genetic characteristics of the human tumor specimens from which they were derived, have intact stromal components, and are more predictive of patient response than traditional models. This review briefly describes the advantages and disadvantages of 2D cultures, organoids and genetically engineered mouse (GEM) models of PDAC, and focuses on the applications, characteristics, advantages, limitations, and the future potential of PDX models for improving the management of PDAC. Full article

(This article belongs to the Special Issue Patient-Derived Xenograft-Models in Cancer Research)

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18 pages, 700 KiB

Open AccessReview

Patient-Derived Xenograft Models in Urological Malignancies: Urothelial Cell Carcinoma and Renal Cell Carcinoma

by Andrew T. Tracey, Katie S. Murray, Jonathan A. Coleman and Kwanghee Kim

Cancers 2020, 12(2), 439; https://doi.org/10.3390/cancers12020439 - 13 Feb 2020

Cited by 10 | Viewed by 4107

Abstract

The engraftment of human tumor tissues into immunodeficient host mice to generate patient-derived xenograft (PDX) models has become increasingly utilized for many types of cancers. By capturing the unique genomic and molecular properties of the parental tumor, PDX models enable analysis of patient-specific [...] Read more.

The engraftment of human tumor tissues into immunodeficient host mice to generate patient-derived xenograft (PDX) models has become increasingly utilized for many types of cancers. By capturing the unique genomic and molecular properties of the parental tumor, PDX models enable analysis of patient-specific clinical responses. PDX models are an important platform to address the contribution of inter-tumoral heterogeneity to therapeutic sensitivity, tumor evolution, and the mechanisms of treatment resistance. With the increasingly important role played by targeted therapies in urological malignancies, the establishment of representative PDX models can contribute to improved facilitation and adoption of precision medicine. In this review of the evolving role of the PDX in urothelial cancer and kidney cancer, we discuss the essential elements of successful graft development, effective translational application, and future directions for clinical models. Full article

(This article belongs to the Special Issue Patient-Derived Xenograft-Models in Cancer Research)

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