Ibrutinib: from bench side to clinical implications.

The activation of the B cell receptor (BCR) is nowadays known to play a primary role in the etiopathogenesis of a multitude of B cell malignancies, being one of the main factors responsible for the enhanced proliferation and survival of transformed cells. Thanks to the characterization and continuous discovery of the pathways driving B cell proliferation in consequence to BCR activation, it has been possible to develop a small molecule inhibitor specifically antagonizing the Bruton's tyrosine kinase (BTK), an enzyme located in an early strategic position within the whole pathway. Ibrutinib, formerly PCI-32765, is a first in class, potent, specific, irreversible and relatively safe BTK inhibitor, demonstrating so far an impressive efficacy in the treatment of chronic lymphocytic leukemia, diffuse large B cell lymphoma, follicular lymphoma, mantle cell lymphoma (MCL), Waldenström macroglobulinemia and multiple myeloma.