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      Syk inhibitors in clinical development for hematological malignancies

      review-article
      Author(s): 1 , , 2
      Publication date (Electronic):
      Journal: Journal of Hematology & Oncology
      Publisher: BioMed Central

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          Abstract

          Spleen tyrosine kinase (Syk) is a cytosolic non-receptor protein tyrosine kinase (PTK) and is mainly expressed in hematopoietic cells. Syk was recognized as a critical element in the B-cell receptor signaling pathway. Syk is also a key component in signal transduction from other immune receptors like Fc receptors and adhesion receptors. Several oral Syk inhibitors including fostamatinib (R788), entospletinib (GS-9973), cerdulatinib (PRT062070), and TAK-659 are being assessed in clinical trials. The second generation compound, entospletinib, showed promising results in clinical trials against B-cell malignancies, mainly chronic lymphoid leukemia. Syk inhibitors are being evaluated in combination regimens in multiple malignancies.

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          Most cited references81

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          Therapeutic T cell engineering

          Michel Sadelain, Isabelle Rivière, Stanley Riddell (2017)
          Genetically engineered T cells are powerful new medicines, offering hope for curative responses in patients with cancer. Chimaeric antigen receptors (CARs) are a class of synthetic receptors that reprogram lymphocyte specificity and function. CARs targeting CD19 have demonstrated remarkable potency in B cell malignancies. Engineered
          Article 0 comments Cited 342 times – based on 0 reviews     Review now
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            Acalabrutinib (ACP-196) in Relapsed Chronic Lymphocytic Leukemia.

            John C. Byrd, Bonnie Harrington, Susan O’Brien … (2016)
            Irreversible inhibition of Bruton's tyrosine kinase (BTK) by ibrutinib represents an important therapeutic advance for the treatment of chronic lymphocytic leukemia (CLL). However, ibrutinib also irreversibly inhibits alternative kinase targets, which potentially compromises its therapeutic index. Acalabrutinib (ACP-196) is a more selective, irreversible BTK inhibitor that is specifically designed to improve on the safety and efficacy of first-generation BTK inhibitors.
            Article 0 comments Cited 312 times – based on 0 reviews     Review now
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              Immune thrombocytopenic purpura.

              Douglas Cines, Victor Blanchette (2002)
              Article 0 comments Cited 210 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Delong Liu:
                ORCID: http://orcid.org/0000-0003-4502-4949
                delong_liu@nymc.edu
                Journal
                Journal ID (nlm-ta): J Hematol Oncol
                Journal ID (iso-abbrev): J Hematol Oncol
                Title: Journal of Hematology & Oncology
                Publisher: BioMed Central (London )
                ISSN (Electronic): 1756-8722
                Publication date (Electronic): 28 July 2017
                Publication date PMC-release: 28 July 2017
                Publication date Collection: 2017
                Volume: 10
                Electronic Location Identifier: 145
                Affiliations
                [1 ]GRID grid.412633.1, Department of Oncology, , The first Affiliated Hospital of Zhengzhou University, ; Zhengzhou, 450052 China
                [2 ]ISNI 0000 0004 0476 8324, GRID grid.417052.5, , Department of Medicine, New York Medical College and Westchester Medical Center, ; Valhalla, NY 10595 USA
                Author information
                http://orcid.org/0000-0003-4502-4949
                Article
                Publisher ID: 512
                DOI: 10.1186/s13045-017-0512-1
                PMC ID: 5534090
                PubMed ID: 28754125
                SO-VID: dc6064d9-48b7-4fdf-81b5-4cc9e0f5b61d
                Copyright © © The Author(s). 2017
                License:

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                Date received : 29 April 2017
                Date accepted : 20 July 2017
                Categories
                Subject: Review
                Custom metadata
                issue-copyright-statement © The Author(s) 2017

                ScienceOpen disciplines: Oncology & Radiotherapy
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy

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