Tumor Xenografts

A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: closed (31 May 2019) | Viewed by 13446

Special Issue Editors


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Guest Editor
Department of Immunology, Roswell Park Cancer Institute, Buffalo, United States
Interests: mouse models, tumor immunology, stress, housing temperature

E-Mail Website
Guest Editor
Department of Immunology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA
Interests: stress and tumor immunity; thermal stress; immunotherapy; tumor microenvironment and physiology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleague,

Mouse models are used in preclinical and translational research to investigate events that initiate and drive cancer progression, as well as to evaluate new therapies. There is a wide spectrum of mouse models to choose from, depending on the intended experimental purpose. However, there is a growing realization that the therapeutic results obtained using mouse models often do not predict efficacy in the clinic. One approach to improving the modeling of patient tumors and their therapeutic responses has been to develop cohorts of patient-derived xenograft tumors (PDX models). PDX models, engrafted into immunodeficient SCID mice, are thought to best represent the diversity and heterogeneity of the patient population. A major shortcoming of these models is the lack of adaptive immune responses in SCID mice, although this is being addressed by the use of so-called humanized SCID mice. The current status of PDX models is the focus of this Special Issue. We welcome articles that will review and present up-to-date information on the characterization and advantages of PDX models, especially as to how well they actually recapitulate the diversity of patient tumors, the evaluation of new therapeutics, biomarker discovery, use as avatars in personalized medicine approaches, and ideas as to how to improve these valuable models.

Dr. Bonnie Hylander
Prof. Dr. Elizabeth Repasky
Guest Editors

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Keywords

  • PDX
  • patient xenograft
  • avatar
  • mouse model
  • tumorografts

Published Papers (3 papers)

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Research

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14 pages, 12569 KiB  
Article
Profiling the Stromal and Vascular Heterogeneity in Patient-derived Xenograft Models of Head and Neck Cancer: Impact on Therapeutic Response
by Margaret Folaron, Mihai Merzianu, Umamaheswar Duvvuri, Robert L. Ferris and Mukund Seshadri
Cancers 2019, 11(7), 951; https://doi.org/10.3390/cancers11070951 - 06 Jul 2019
Cited by 9 | Viewed by 3473
Abstract
Head and neck squamous cell carcinomas (HNSCC) represent a group of epithelial neoplasms that exhibit considerable heterogeneity in clinical behavior. Here, we examined the stromal and vascular heterogeneity in a panel of patient-derived xenograft (PDX) models of HNSCC and the impact on therapeutic [...] Read more.
Head and neck squamous cell carcinomas (HNSCC) represent a group of epithelial neoplasms that exhibit considerable heterogeneity in clinical behavior. Here, we examined the stromal and vascular heterogeneity in a panel of patient-derived xenograft (PDX) models of HNSCC and the impact on therapeutic response. Tumor sections from established tumors were stained for p16 (surrogate for human papillomavirus (HPV) infection), stromal (Masson’s trichrome) and vascular (CD31) markers. All PDX models retained the HPV/p16 status of the original patient tumor. Immunohistochemical evaluation revealed the presence of multiple vessel phenotypes (tumor, stromal or mixed) in the PDX panel. Vascular phenotypes identified in the PDX models were validated in a tissue microarray of human HNSCC. Treatment with a microtubule targeted vascular disrupting agent (VDA) resulted in a heterogeneous antivascular and antitumor response in PDX models. The PDX with the tumor vessel phenotype that exhibited higher CD31+ vessel counts and leaky vasculature on magnetic resonance imaging (MRI) was sensitive to VDA treatment while the PDX with the stromal vessel phenotype was resistant to therapy. Collectively, our results demonstrate the phenotypic and functional vascular heterogeneity in HNSCC and highlight the impact of this heterogeneity on response to antivascular therapy in PDX models of HNSCC. Full article
(This article belongs to the Special Issue Tumor Xenografts)
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19 pages, 1709 KiB  
Article
Membrane Lipidome Reorganization and Accumulation of Tissue DNA Lesions in Tumor-Bearing Mice: An Exploratory Study
by Marios G. Krokidis, Maria Louka, Eleni K. Efthimiadou, Sevasti-Kiriaki Zervou, Kyriakos Papadopoulos, Anastasia Hiskia, Carla Ferreri and Chryssostomos Chatgilialoglu
Cancers 2019, 11(4), 480; https://doi.org/10.3390/cancers11040480 - 04 Apr 2019
Cited by 15 | Viewed by 3544
Abstract
Increased rates of reactive oxygen/nitrogen species (ROS/RNS) are involved in almost all cancer types, associated with tumor development and progression, causing damage to biomolecules such as proteins, nucleic acids and membrane lipids, in different biological compartments. We used a human tumor xenograft mouse [...] Read more.
Increased rates of reactive oxygen/nitrogen species (ROS/RNS) are involved in almost all cancer types, associated with tumor development and progression, causing damage to biomolecules such as proteins, nucleic acids and membrane lipids, in different biological compartments. We used a human tumor xenograft mouse model to evaluate for the first time in parallel the remodeling of fatty acid moieties in erythrocyte membrane phospholipids and the level of ROS-induced DNA lesions in liver and kidney tissues. Using liquid chromatography tandem mass spectrometry the 5′R and 5′S diastereoisomers of 5′,8-cyclo-2′-deoxyadenosine and 5′,8-cyclo-2′-deoxyguanosine, together with 8-oxo-7,8-dihydro-2′-deoxyadenosine, were determined in mice at young (4- and 5-weeks) and old (17-weeks) ages and compared with control SCID mice without tumor implantation. Tumor-bearing mice showed a higher level of ROS-damaged nucleosides in genomic DNA as the age and tumor progress, compared to controls (1.07–1.53-fold in liver and 1.1–1.4-fold in kidney, respectively). The parallel fatty acid profile of erythrocyte membranes showed a profound lipid remodeling during tumor and age progression consisting of PUFA consumption and SFA enrichment (ca 28% and 58%, respectively, in late stage tumor-bearing mice), markers of enhanced oxidative and proliferative processes, respectively. Membrane lipid remodeling and ROS-induced DNA lesions may be combined to afford an integrated scenario of cancer progression and ageing, reinforcing a holistic vision among molecular markers rather than the biomarker identification in a single compartment. Full article
(This article belongs to the Special Issue Tumor Xenografts)
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Review

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24 pages, 855 KiB  
Review
Current and Future Horizons of Patient-Derived Xenograft Models in Colorectal Cancer Translational Research
by Akira Inoue, Angela K. Deem, Scott Kopetz, Timothy P. Heffernan, Giulio F. Draetta and Alessandro Carugo
Cancers 2019, 11(9), 1321; https://doi.org/10.3390/cancers11091321 - 06 Sep 2019
Cited by 30 | Viewed by 5961
Abstract
Our poor understanding of the intricate biology of cancer and the limited availability of preclinical models that faithfully recapitulate the complexity of tumors are primary contributors to the high failure rate of novel therapeutics in oncology clinical studies. To address this need, patient-derived [...] Read more.
Our poor understanding of the intricate biology of cancer and the limited availability of preclinical models that faithfully recapitulate the complexity of tumors are primary contributors to the high failure rate of novel therapeutics in oncology clinical studies. To address this need, patient-derived xenograft (PDX) platforms have been widely deployed and have reached a point of development where we can critically review their utility to model and interrogate relevant clinical scenarios, including tumor heterogeneity and clonal evolution, contributions of the tumor microenvironment, identification of novel drugs and biomarkers, and mechanisms of drug resistance. Colorectal cancer (CRC) constitutes a unique case to illustrate clinical perspectives revealed by PDX studies, as they overcome limitations intrinsic to conventional ex vivo models. Furthermore, the success of molecularly annotated "Avatar" models for co-clinical trials in other diseases suggests that this approach may provide an additional opportunity to improve clinical decisions, including opportunities for precision targeted therapeutics, for patients with CRC in real time. Although critical weaknesses have been identified with regard to the ability of PDX models to predict clinical outcomes, for now, they are certainly the model of choice for preclinical studies in CRC. Ongoing multi-institutional efforts to develop and share large-scale, well-annotated PDX resources aim to maximize their translational potential. This review comprehensively surveys the current status of PDX models in translational CRC research and discusses the opportunities and considerations for future PDX development. Full article
(This article belongs to the Special Issue Tumor Xenografts)
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