Inhibition of B Cell Receptor Signaling: A First Targeted Therapeutic Approach for Chronic Lymphocytic Leukemia and Other B Cell Lymphomas

Česká verzia

Authors: Mráz M. ^1–3; M. Doubek ^1,2; J. Mayer ^1,2
Authors place of work: Interní hematologická a onkologická klinika LF MU a FN Brno ¹; CEITEC – Středoevropský technologický institut, MU, Brno ²; University of California‑ San Diego, Moores Cancer Center, La Jolla, CA, USA ³
Published in the journal: Klin Onkol 2013; 26(3): 179-185
Category: Review

Summary

Chronic lymphocytic leukemia (CLL) is the most frequent, yet by conventional therapy still incurable, leukemia in the Western world. Accumulating evidence of the role of B cell receptor (BCR) pathway in CLL B cell biology suggests the possible use of ’BCR inhibitors’ for targeted therapy. Recently published results of clinical trials of three different molecules (fosfamatinib, ibrutinib and GS‑ 1101) targeting BCR‑associated kinases (Syk, Btk, PI3K) showed impressive clinical activity in CLL. These findings will likely modify treatment approaches for chronic lymphocytic leukemia and some other B cell lymphomas in the near future. Herein, we review the data on BCR pathway deregulation in malignant CLL B cells, and the results of clinical trials utilizing fosfamatinib, ibrutinib and GS‑ 1101.

Key words:
BCR signaling – B cell receptor – Btk protein – Syk protein – Lyn protein – PI3K – CAL‑ 101 – PCI‑ 32765 – R788

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