INTRODUCTION: There has been a significant paradigm shift in the manner in which 
lymphoid malignancies are treated and managed. Treatment has been moving away 
from conventional chemotherapy and towards targeted therapy. The success of new 
classes of agents such as monoclonal antibodies, proteasome inhibitors and 
immunomodulatory derivatives has sparked further searches for novel pathways to 
inhibit. The Bruton's tyrosine kinase (Btk) pathway is a downstream mediator of 
the B-cell receptor (BCR) pathway, which is crucial in B-cell production and 
maintenance, and a potential therapeutic target.
AREAS COVERED: This review will summarize the current knowledge of the Btk 
pathway and its role in lymphoid malignancies. It will also discuss the present 
data about PCI-32765 in both the preclinical and clinical setting.
EXPERT OPINION: PCI-32765 is an oral irreversible Btk inhibitor with high 
potency and both preclinical and clinical activity in chronic lymphocytic 
leukemia (CLL) and non-Hodgkin's lymphoma (NHL). Phase I studies have 
demonstrated that it is well tolerated and has an excellent safety profile. 
Further studies are ongoing as a single agent and in combination with other 
targeted and conventional therapies. PCI-32765 is a very promising targeted 
therapy, and the data from these trials will ultimately decide its future role 
and success.