Targeting Brutons tyrosine kinase signaling as an emerging…针对布鲁克斯酪氨酸激酶信号作为一种新兴的.pdfVIP

ONCOLOGY LETTERS 10: 3339-3344, 2015 Targeting Brutons tyrosine kinase signaling as an emerging therapeutic agent of B‑cell malignancies (Review) * * BING XIA , FULIAN QU , TIAN YUAN and YIZHUO ZHANG Department of Hematology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, P.R. China Received November 4, 2014; Accepted September 14, 2015 DOI: 10.3892/ol.2015.3802 Abstract. It is becoming increasingly evident that B-cell 1. Introduction receptor (BCR) signaling is central to the development and function of B cells. BCR signaling has emerged as a pivotal B-cell malignancies are a heterogeneous group of disorders pathway and a key driver of numerous B-cell lymphomas. and treatment of these conditions has essentially remained Disruption of BCR signaling can be lethal to malignant B cells. the same for 30 years, with the exception of the inclusion Recently, kinase inhibitors that target BCR signaling have of monoclonal anti-cluster of differentiation (CD)20 agents in induced notable clinical responses. These inhibitors include combination strategies (1,2). A pivotal moment in the develop- spleen tyrosine kinase, mammalian target of rapamycin, phos- ment of novel drugs for this group of disorders arose with the phoinositide 3-kinase and Brutons tyrosine kinase (BTK). introduction of the first biologic targeted agent, the anti‑CD20 Ibrutinib, an oral irreversible BTK inhibitor, has emerged as a monoclonal antibody rituximab, with improved outcomes