<abstract xmlns="http://www.w3.org/1999/xhtml"><p>In normal B-cells, Bruton tyrosine kinase (Btk), a non-receptor tyrosine kinase involved in B-cell receptor (BCR) signalling, is essential for cell survival and maturation. Not surprisingly, Btk is also implicated in the pathogenesis of B-cell lymphomas, like Chronic Lymphocytic Leukaemia/Small Lymphocytic Lymphoma (CLL/SLL), Mantle Cell Lymphoma (MCL) and Waldenström’s Macroglobulinemia (WM), which are driven by aberrant BCR signalling. Thus, targeting Btk represents a promising therapeutic strategy in the treatment of B-cell lymphoma patients. Ibrutinib, a selective Btk inhibitor, has already been approved as second-line treatment of CLL/SLL, MCL and WM patients, while more clinical studies of ibrutinib and novel Btk inhibitors are currently under way. In light of results of the RESONATE-2 trial, the approval of ibrutinib as a first-line treatment of CLL/SLL may well be approaching. Herein, we review Btk’s role in normal and malignant BCR signalling, as well as ibrutinib’s performance in B-cell lymphoma treatment and prognosis.</p></abstract>

In normal B-cells, Bruton tyrosine kinase (Btk), a non-receptor tyrosine kinase involved in B-cell receptor (BCR) signalling, is essential for cell survival and maturation. Not surprisingly, Btk is also implicated in the pathogenesis of B-cell lymphomas, like Chronic Lymphocytic Leukaemia/Small Lymphocytic Lymphoma (CLL/SLL), Mantle Cell Lymphoma (MCL) and Waldenström’s Macroglobulinemia (WM), which are driven by aberrant BCR signalling. Thus, targeting Btk represents a promising therapeutic strategy in the treatment of B-cell lymphoma patients. Ibrutinib, a selective Btk inhibitor, has already been approved as second-line treatment of CLL/SLL, MCL and WM patients, while more clinical studies of ibrutinib and novel Btk inhibitors are currently under way. In light of results of the RESONATE-2 trial, the approval of ibrutinib as a first-line treatment of CLL/SLL may well be approaching. Herein, we review Btk’s role in normal and malignant BCR signalling, as well as ibrutinib’s performance in B-cell lymphoma treatment and prognosis.

Targeting Bruton Tyrosine Kinase: A novel strategy in the treatment of B-cell lymphomas

Forum of Clinical Oncology

This article is distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

In normal B-cells, Bruton tyrosine kinase (Btk), a non-receptor tyrosine kinase involved in B-cell receptor (BCR) signalling, is essential for cell survival...

Targeting Bruton Tyrosine Kinase: A novel strategy in the treatment of B-cell lymphomas

Published Online: Jun 30, 2017

Page range: 7 - 14

Received: Sep 08, 2016

Accepted: Aug 24, 2017

DOI: https://doi.org/10.1515/fco-2015-0026

Keywords
Bruton, tyrosine, kinase, inhibitor, ibrutinib, BCR, lymphoma, CLL, treatment

© 2017 Sklavenitis-Pistofidis R., Koletsa T., Lazaridou A., Goulas A.

This article is distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Targeting Bruton Tyrosine Kinase: A novel strategy in the treatment of B-cell lymphomas

Published Online: Jun 30, 2017

Page range: 7 - 14

Received: Sep 08, 2016

Accepted: Aug 24, 2017

DOI: https://doi.org/10.1515/fco-2015-0026

KeywordsBruton, tyrosine, kinase, inhibitor, ibrutinib, BCR, lymphoma, CLL, treatment

© 2017 Sklavenitis-Pistofidis R., Koletsa T., Lazaridou A., Goulas A.

This article is distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Keywords
Bruton, tyrosine, kinase, inhibitor, ibrutinib, BCR, lymphoma, CLL, treatment