title: Targeting Bruton's tyrosine kinase signaling as an emerging therapeutic agent of B-cell malignancies.
abstract: It is becoming increasingly evident that B-cell receptor (BCR) signaling is central to the development and function of B cells. BCR signaling has emerged as a pivotal pathway and a key driver of numerous B-cell lymphomas. Disruption of BCR signaling can be lethal to malignant B cells. Recently, kinase inhibitors that target BCR signaling have induced notable clinical responses. These inhibitors include spleen tyrosine kinase, mammalian target of rapamycin, phosphoinositide 3'-kinase and Bruton's tyrosine kinase (BTK). Ibrutinib, an oral irreversible BTK inhibitor, has emerged as a promising targeted therapy for patients with B-cell malignancies. The present review discusses the current understanding of BTK-mediated BCR signaling in the biology and pathobiology of normal and malignant B cells, and the cellular interaction with the tumor microenvironment. The data on ibrutinib in the preclinical and clinical settings is also discussed, and perspectives for the future use of ibrutinib are outlined.
authors.affiliation: 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.
authors.forename: Bing
authors.initials: B
authors.lastname: Xia
authors.affiliation: 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.
authors.forename: Fulian
authors.initials: F
authors.lastname: Qu
authors.affiliation: 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.
authors.forename: Tian
authors.initials: T
authors.lastname: Yuan
authors.affiliation: 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.
authors.forename: Yizhuo
authors.initials: Y
authors.lastname: Zhang
keywords: B-cell malignancies; ibrutinib; signal transducing; treatment; tumor microenvironment