Ibrutinib in chronic lymphocytic leukemia

Abstract

Chronic lymphocytic leukemia is a mature B-cell neoplasm in which the interactions between the malignant B cells and tumor microenvironment play a key role in cell survival and growth. B-cell receptor (BCR) is a key survival pathway in chronic lymphocytic leukemia. Following BCR signal trigger, several kinase pathways are activated that promote signal transduction. Ibrutinib is a first-in-class, potent, orally administered covalently binding inhibitor of Bruton's tyrosine kinase that is US FDA approved. Inhibition of Bruton's tyrosine kinase blocks downstream BCR signaling pathways (AKT, ERK) and thus prevents B-cell proliferation. Ibrutinib impairs microenvironment-induced survival of the malignant B cells. Ibrutinib is currently under investigation for both hematologic and solid tumor malignancies.