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Review
. 2014 Aug;5(4):121-33.
doi: 10.1177/2040620714539906.

Bruton's tyrosine kinase inhibitors and their clinical potential in the treatment of B-cell malignancies: focus on ibrutinib

Amin Aalipour  1 , Ranjana H Advani  2
Affiliations
Review

Bruton's tyrosine kinase inhibitors and their clinical potential in the treatment of B-cell malignancies: focus on ibrutinib

Amin Aalipour et al. Ther Adv Hematol. 2014 Aug.

Abstract

Aberrant signaling of the B-cell receptor pathway has been linked to the development and maintenance of B-cell malignancies. Bruton's tyrosine kinase (BTK), a protein early in this pathway, has emerged as a new therapeutic target in a variety of such malignancies. Ibrutinib, the most clinically advanced small molecule inhibitor of BTK, has demonstrated impressive tolerability and activity in a range of B-cell lymphomas which led to its recent approval for relapsed mantle cell lymphoma and chronic lymphocytic leukemia. This review focuses on the preclinical and clinical development of ibrutinib and discusses its therapeutic potential.

Keywords: B-cell receptor signaling; Bruton’s tyrosine kinase; chronic lymphocytic leukemia; ibrutinib; mantle cell lymphoma; refractory non-Hodgkin’s lymphoma.

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Conflict of interest statement

Conflict of interest statement: Amin Aalipour declares no conflict of interests. Ranjana H. Advani has received research funding from Pharmacyclics, Inc. and Janssen Pharmaceuticals, Inc.

Figures

Figure 1.
Figure 1.
The B cell receptor signalling pathway controls B-cell fate and function. Reprinted from Aalipour and Advani [2013] with permission from Wiley. BTK, Bruton’s tyrosine kinase; IKK, IκB Kinase MAPK, mitogen-activated protein kinase; NFκB, nuclear factor κB; PI3Kδ, phosphoinositide 3-kinase; PIP2, phosphatidylinositol 4,5 bisphosphate; PIP3, phosphatidylinositol 3,4,5 triphosphate; PKC, protein kinase C; PLCγ2, phospholipase C γ2.
See this image and copyright information in PMC

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