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      Bruton's tyrosine kinase (BTK) inhibitors in clinical trials.

      1
      Current hematologic malignancy reports
      Springer Science and Business Media LLC

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          Abstract

          BTK is a cytoplasmic, non-receptor tyrosine kinase that transmits signals from a variety of cell-surface molecules, including the B-cell receptor (BCR) and tissue homing receptors. Genetic BTK deletion causes B-cell immunodeficiency in humans and mice, making this kinase an attractive therapeutic target for B-cell disorders. The BTK inhibitor ibrutinib (PCI-32765, brand name: Imbruvica) demonstrated high clinical activity in B-cell malignancies, especially in patients with chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), and Waldenstrom's macroglobulinemia (WM). Therefore, ibrutinib was granted a 'breakthrough therapy' designation for these indications and was recently approved for the treatment of relapsed MCL by the U.S. Food and Drug Administration. Other BTK inhibitors in earlier clinical development include CC-292 (AVL-292), and ONO-4059. In CLL and MCL, ibrutinib characteristically induces redistribution of malignant B cells from tissue sites into the peripheral blood, along with rapid resolution of enlarged lymph nodes and a surge in lymphocytosis. With continuous ibrutinib therapy, growth- and survival-inhibitory activities of ibrutinib result in the normalization of lymphocyte counts and remissions in a majority of patients. This review discusses the clinical advances with BTK inhibitor therapy, as well as its pathophysiological basis, and outlines perspectives for future use of BTK inhibitors.

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          Author and article information

          Journal
          Curr Hematol Malig Rep
          Current hematologic malignancy reports
          Springer Science and Business Media LLC
          1558-822X
          1558-8211
          Mar 2014
          : 9
          : 1
          Affiliations
          [1 ] Department of Leukemia, The University of Texas MD Anderson Cancer Center, Unit 428, PO Box 301402, Houston, TX, 77230-1402, USA, jaburger@mdanderson.org.
          Article
          10.1007/s11899-013-0188-8
          24357428
          dc4bf88d-f964-4fd6-a57b-9323b87e1357
          History

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