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B cell receptor pathway in chronic lymphocytic leukemia: specific role of CC-292

Authors Arnason J, Brown J

Received 3 October 2013

Accepted for publication 13 November 2013

Published 24 January 2014 Volume 2014:3 Pages 29—38

DOI https://doi.org/10.2147/ITT.S37419

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3


Jon E Arnason,1 Jennifer R Brown2

1Beth Israel Deaconess Medical Center, 2CLL Center, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA

Abstract: Chronic lymphocytic leukemia (CLL) is the most common adult leukemia. The current treatment paradigm involves the use of chemoimmunotherapy, when patients develop an indication for therapy. With this strategy, a majority of patients will obtain a remission, though cure remains elusive. While treatable, the majority of CLL patients will die of complications of their disease. Recent advances in the understanding of the importance of the B cell receptor (BCR) pathway in CLL have led to the development of a number of agents targeting this pathway. In this review, we discuss recent developments in the targeting of the BCR pathway, with a focus on CC-292. CC-292 covalently binds to Bruton's tyrosine kinase, a key mediator of BCR signaling, and has demonstrated preclinical and clinical activity in CLL, with acceptable tolerability. Based on the success of CC-292 and other inhibitors of the BCR pathway, these agents are being investigated in combination with standard therapy, with the hope that they will increase the depth and length of response, without significant toxicity.

Keywords: Bruton's tyrosine kinase inhibitor, ibrutinib

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