Bruton's Tyrosine Kinase: From X-Linked Agammaglobulinemia Toward Targeted Therapy for B-Cell Malignancies

Discovery of Bruton's tyrosine kinase (BTK) mutations as the cause for X-linked agammaglobulinemia was a milestone in understanding the genetic basis of primary immunodeficiencies. Since then, studies have highlighted the critical role of this enzyme in B-cell development and function, and part...

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Veröffentlicht in:Journal of clinical oncology 2014-06, Vol.32 (17), p.1830-1839
Hauptverfasser: PONADER, Sabine, BURGER, Jan A
Format: Artikel
Sprache:eng
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Zusammenfassung:Discovery of Bruton's tyrosine kinase (BTK) mutations as the cause for X-linked agammaglobulinemia was a milestone in understanding the genetic basis of primary immunodeficiencies. Since then, studies have highlighted the critical role of this enzyme in B-cell development and function, and particularly in B-cell receptor signaling. Because its deletion affects mostly B cells, BTK has become an attractive therapeutic target in autoimmune disorders and B-cell malignancies. Ibrutinib (PCI-32765) is the most advanced BTK inhibitor in clinical testing, with ongoing phase III clinical trials in patients with chronic lymphocytic leukemia and mantle-cell lymphoma. In this article, we discuss key discoveries related to BTK and clinically relevant aspects of BTK inhibitors, and we provide an outlook into clinical development and open questions regarding BTK inhibitor therapy.
ISSN:0732-183X
1527-7755
DOI:10.1200/jco.2013.53.1046