Bruton tyrosine kinase inhibitors: a promising novel targeted treatment for B cell lymphomas

Br J Haematol. 2013 Nov;163(4):436-43. doi: 10.1111/bjh.12573. Epub 2013 Sep 24.

Abstract

Constitutive or aberrant signalling of the B cell receptor signalling cascade has been implicated in the propagation and maintenance of a variety of B cell malignancies. Small molecule inhibitors of Bruton tyrosine kinase (BTK), a protein early in this cascade and specifically expressed in B cells, have emerged as a new class of targeted agents. There are several BTK inhibitors, including ONO-WG-307, LFM-A13, dasatinib, CC-292, and PCI-32765 (ibrutinib), in preclinical and/or clinical development of which ibrutinib is currently in phase III trials. Recent clinical data suggest significant activity of ibrutinib as a first in class oral inhibitor of BTK. This review provides an overview of ongoing clinical studies of BTK inhibitors.

Keywords: B cell receptor signalling; Bruton tyrosine kinase; CC-292; ibrutinib; refractory non-Hodgkin lymphoma.

Publication types

  • Review

MeSH terms

  • Adenine / analogs & derivatives
  • Agammaglobulinaemia Tyrosine Kinase
  • Animals
  • Humans
  • Lymphoma, B-Cell / drug therapy*
  • Lymphoma, B-Cell / enzymology*
  • Lymphoma, B-Cell / pathology
  • Molecular Targeted Therapy
  • Piperidines
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use*
  • Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Pyrazoles / pharmacology
  • Pyrazoles / therapeutic use
  • Pyrimidines / pharmacology
  • Pyrimidines / therapeutic use

Substances

  • Piperidines
  • Protein Kinase Inhibitors
  • Pyrazoles
  • Pyrimidines
  • ibrutinib
  • Protein-Tyrosine Kinases
  • Agammaglobulinaemia Tyrosine Kinase
  • BTK protein, human
  • Adenine