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Naturally-Occurring Canine Invasive Urothelial Carcinoma: A Model for Emerging Therapies

The development of targeted therapies and the resurgence of immunotherapy offer enormous potential to dramatically improve the outlook for patients with invasive urothelial carcinoma (InvUC). Optimization of these therapies, however, is crucial as only a minority of patients achieve dramatic remissi...

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Autores principales: Sommer, Breann C., Dhawan, Deepika, Ratliff, Timothy L., Knapp, Deborah W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: IOS Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5929349/
https://www.ncbi.nlm.nih.gov/pubmed/29732386
http://dx.doi.org/10.3233/BLC-170145
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author Sommer, Breann C.
Dhawan, Deepika
Ratliff, Timothy L.
Knapp, Deborah W.
author_facet Sommer, Breann C.
Dhawan, Deepika
Ratliff, Timothy L.
Knapp, Deborah W.
author_sort Sommer, Breann C.
collection PubMed
description The development of targeted therapies and the resurgence of immunotherapy offer enormous potential to dramatically improve the outlook for patients with invasive urothelial carcinoma (InvUC). Optimization of these therapies, however, is crucial as only a minority of patients achieve dramatic remission, and toxicities are common. With the complexities of the therapies, and the growing list of possible drug combinations to test, highly relevant animal models are needed to assess and select the most promising approaches to carry forward into human trials. The animal model(s) should possess key features that dictate success or failure of cancer drugs in humans including tumor heterogeneity, genetic-epigenetic crosstalk, immune cell responsiveness, invasive and metastatic behavior, and molecular subtypes (e.g., luminal, basal). While it may not be possible to create these collective features in experimental models, these features are present in naturally-occurring InvUC in pet dogs. Naturally occurring canine InvUC closely mimics muscle-invasive bladder cancer in humans in regards to cellular and molecular features, molecular subtypes, biological behavior (sites and frequency of metastasis), and response to therapy. Clinical treatment trials in pet dogs with InvUC are considered a win-win scenario; the individual dog benefits from effective treatment, the results are expected to help other dogs, and the findings are expected to translate to better treatment outcomes in humans. This review will provide an overview of canine InvUC, the similarities to the human condition, and the potential for dogs with InvUC to serve as a model to predict the outcomes of targeted therapy and immunotherapy in humans.
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spelling pubmed-59293492018-05-03 Naturally-Occurring Canine Invasive Urothelial Carcinoma: A Model for Emerging Therapies Sommer, Breann C. Dhawan, Deepika Ratliff, Timothy L. Knapp, Deborah W. Bladder Cancer Review The development of targeted therapies and the resurgence of immunotherapy offer enormous potential to dramatically improve the outlook for patients with invasive urothelial carcinoma (InvUC). Optimization of these therapies, however, is crucial as only a minority of patients achieve dramatic remission, and toxicities are common. With the complexities of the therapies, and the growing list of possible drug combinations to test, highly relevant animal models are needed to assess and select the most promising approaches to carry forward into human trials. The animal model(s) should possess key features that dictate success or failure of cancer drugs in humans including tumor heterogeneity, genetic-epigenetic crosstalk, immune cell responsiveness, invasive and metastatic behavior, and molecular subtypes (e.g., luminal, basal). While it may not be possible to create these collective features in experimental models, these features are present in naturally-occurring InvUC in pet dogs. Naturally occurring canine InvUC closely mimics muscle-invasive bladder cancer in humans in regards to cellular and molecular features, molecular subtypes, biological behavior (sites and frequency of metastasis), and response to therapy. Clinical treatment trials in pet dogs with InvUC are considered a win-win scenario; the individual dog benefits from effective treatment, the results are expected to help other dogs, and the findings are expected to translate to better treatment outcomes in humans. This review will provide an overview of canine InvUC, the similarities to the human condition, and the potential for dogs with InvUC to serve as a model to predict the outcomes of targeted therapy and immunotherapy in humans. IOS Press 2018-04-26 /pmc/articles/PMC5929349/ /pubmed/29732386 http://dx.doi.org/10.3233/BLC-170145 Text en © 2018 – IOS Press and the authors. All rights reserved https://creativecommons.org/licenses/by-nc/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial (CC BY-NC 4.0) License (https://creativecommons.org/licenses/by-nc/4.0/) , which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review
Sommer, Breann C.
Dhawan, Deepika
Ratliff, Timothy L.
Knapp, Deborah W.
Naturally-Occurring Canine Invasive Urothelial Carcinoma: A Model for Emerging Therapies
title Naturally-Occurring Canine Invasive Urothelial Carcinoma: A Model for Emerging Therapies
title_full Naturally-Occurring Canine Invasive Urothelial Carcinoma: A Model for Emerging Therapies
title_fullStr Naturally-Occurring Canine Invasive Urothelial Carcinoma: A Model for Emerging Therapies
title_full_unstemmed Naturally-Occurring Canine Invasive Urothelial Carcinoma: A Model for Emerging Therapies
title_short Naturally-Occurring Canine Invasive Urothelial Carcinoma: A Model for Emerging Therapies
title_sort naturally-occurring canine invasive urothelial carcinoma: a model for emerging therapies
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5929349/
https://www.ncbi.nlm.nih.gov/pubmed/29732386
http://dx.doi.org/10.3233/BLC-170145
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