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      Comparative oncology: The paradigmatic example of canine and human mast cell neoplasms

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          Abstract

          In humans, advanced mast cell (MC) neoplasms are rare malignancies with a poor prognosis. Only a few preclinical models are available, and current treatment options are limited. In dogs, MC neoplasms are the most frequent malignant skin tumours. Unlike low‐grade MC neoplasms, high‐grade MC disorders usually have a poor prognosis with short survival. In both species, neoplastic MCs display activating KIT mutations, which are considered to contribute to disease evolution. Therefore, tyrosine kinase inhibitors against KIT have been developed. Unfortunately, clinical responses are unpredictable and often transient, which remains a clinical challenge in both species. Therefore, current efforts focus on the development of new improved treatment strategies. The field of comparative oncology may assist in these efforts and accelerate human and canine research regarding diagnosis, prognostication, and novel therapies. In this article, we review the current status of comparative oncology approaches and perspectives in the field of MC neoplasms.

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          Most cited references75

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          Mastocytosis 2016: Updated WHO Classification and Novel Emerging Treatment Concepts.

          Over the past few years substantial advances have been made in understanding the pathogenesis, evolution, and complexity of mast cell neoplasms. New diagnostic and prognostic parameters and novel therapeutic targets with demonstrable clinical impact have been identified. A number of these new markers, molecular targets, and therapeutic approaches have been validated and translated into clinical practice. At the same time, the classification of mastocytosis and related diagnostic criteria have been refined and updated by the consensus group and the World Health Organization (WHO). As a result, more specific therapies tailored towards prognostic sub-groups of patients have been developed. Emerging treatment concepts employ drugs directed against KIT and other relevant targets in neoplastic mast cells, and will hopefully receive recognition by health authorities in the near future. The current article provides an overview of recent developments in the field, with emphasis on the updated WHO classification, refined criteria, additional prognostic parameters, and novel therapeutic approaches. Based on these emerging concepts, the prognosis, quality of life, and survival of patients with advanced mastocytosis are expected to improve in the coming years.
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            Standards and standardization in mastocytosis: consensus statements on diagnostics, treatment recommendations and response criteria.

            Although a classification for mastocytosis and diagnostic criteria are available, there remains a need to define standards for the application of diagnostic tests, clinical evaluations, and treatment responses. To address these demands, leading experts discussed current issues and standards in mastocytosis in a Working Conference. The present article provides the resulting outcome with consensus statements, which focus on the appropriate application of clinical and laboratory tests, patient selection for interventional therapy, and the selection of appropriate drugs. In addition, treatment response criteria for the various clinical conditions, disease-specific symptoms, and specific pathologies are provided. Resulting recommendations and algorithms should greatly facilitate the management of patients with mastocytosis in clinical practice, selection of patients for therapies, and the conduct of clinical trials.
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              Mast cells and mastocytosis.

              Mast cells have been recognized for well over 100 years. With time, human mast cells have been documented to originate from CD34+ cells, and have been implicated in host responses in both innate and acquired immunity. In clinical immunology, they are recognized for their central role in IgE-mediated degranulation and allergic inflammation by virtue of their expression of the high-affinity receptor for IgE and release of potent proinflammatory mediators. In hematology, the clinical disease of mastocytosis is characterized by a pathologic increase of mast cells in tissues, often associated with mutations in KIT, the receptor for stem cell factor. More recently, and with increased understanding of how human mast cells are activated through receptors including the high-affinity receptor for IgE and KIT, specific tyrosine kinase inhibitors have been identified with the potential to interrupt signaling pathways and thus limit the proliferation of mast cells as well as their activation through immunoglobulin receptors.
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                Author and article information

                Contributors
                michael.willmann@vetmeduni.ac.at
                Journal
                Vet Comp Oncol
                Vet Comp Oncol
                10.1111/(ISSN)1476-5829
                VCO
                Veterinary and Comparative Oncology
                Blackwell Publishing Ltd (Oxford, UK )
                1476-5810
                1476-5829
                24 September 2018
                March 2019
                : 17
                : 1 ( doiID: 10.1111/vco.2019.17.issue-1 )
                : 1-10
                Affiliations
                [ 1 ] Department of Companion Animals and Horses, Clinic for Internal Medicine University of Veterinary Medicine Vienna Vienna Austria
                [ 2 ] Ludwig Boltzmann Cluster Oncology Medical University of Vienna Vienna Austria
                [ 3 ] Department of Medicine I Division of Hematology and Hemostaseology, Medical University of Vienna Vienna Austria
                [ 4 ] Department of Hematology, Necker Hospital Imagine Institute Université Paris Descartes, Sorbonne Paris France
                [ 5 ] Department of Comparative Biomedicine and Food Science University of Padua Padua Italy
                [ 6 ] Centro Oncologico Veterinario Sasso Marconi Italy
                [ 7 ] Institute of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology and Immunology Medical University of Vienna Vienna Austria
                [ 8 ] The Interuniversity Messerli Research Institute University of Veterinary Medicine Vienna, Medical University Vienna, University of Vienna Vienna Austria
                [ 9 ] Biomodels Austria and Institute of Animal Breeding and Genetics University of Veterinary Medicine Vienna Austria
                [ 10 ] LBPA CNRS UMR8113, Ecole Normale Supérieure de Cachan Cachan France
                [ 11 ] Laboratory of Hematology Pitié‐Salpêtrière Hospital Paris France
                [ 12 ] Department of Medical Sciences, School of Veterinary Medicine University of Wisconsin‐Madison Madison Wisconsin
                [ 13 ] Carbone Cancer Center University of Wisconsin‐Madison Madison Wisconsin
                Author notes
                [*] [* ] Correspondence

                Michael Willmann, Oncology Unit, Clinic for Internal Medicine and Ludwig Boltzmann Cluster Oncology, University of Veterinary Medicine Vienna, Veterinärplatz 1, A‐1210 Vienna, Austria.

                Email: michael.willmann@ 123456vetmeduni.ac.at

                Author information
                https://orcid.org/0000-0002-4260-1491
                https://orcid.org/0000-0001-7409-4204
                https://orcid.org/0000-0003-2574-3874
                https://orcid.org/0000-0002-3637-5643
                https://orcid.org/0000-0002-7843-615X
                https://orcid.org/0000-0001-9927-042X
                https://orcid.org/0000-0001-5701-5412
                https://orcid.org/0000-0002-6509-2810
                https://orcid.org/0000-0003-2735-4645
                https://orcid.org/0000-0003-4019-5765
                https://orcid.org/0000-0002-7879-3552
                https://orcid.org/0000-0001-6714-7478
                https://orcid.org/0000-0003-0456-5095
                Article
                VCO12440
                10.1111/vco.12440
                6378619
                30136349
                7745fd24-16fa-42b3-a8ad-37b57f29478b
                © 2018 The Authors. Veterinary and Comparative Oncology published by John Wiley & Sons Ltd.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 20 March 2018
                : 14 August 2018
                : 16 August 2018
                Page count
                Figures: 1, Tables: 4, Pages: 10, Words: 8816
                Funding
                Funded by: Austrian Science Fund
                Award ID: P‐25937‐B13SFB
                Award ID: F4701‐B20SFB
                Award ID: F4704‐B20SFB
                Award ID: F6101SFB F6106
                Categories
                Review Article
                Review Article
                Custom metadata
                2.0
                vco12440
                March 2019
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.5.9 mode:remove_FC converted:18.02.2019

                canine mast cell neoplasm,cd25,cd30,kit mutations,tryptase
                canine mast cell neoplasm, cd25, cd30, kit mutations, tryptase

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