Current research in lymphoma is focused on two areas of lymphoma biology-the 
signal transduction pathways used to maintain the growth of malignant 
lymphocytes and the role of the tumor microenvironment in lymphoma growth and 
survival. This review focuses on three signaling pathways: the 
phosphatidylinositol 3-kinase/mammalian target of rapamycin (PI3K/mTOR) pathway, 
the B-cell receptor/spleen tyrosine kinase (BCR/Syk) pathway, and the protein 
kinase C-beta (PKC-β) pathway, known to be important to lymphoma cells. The mTOR 
inhibitors temsirolimus and everolimus have demonstrated antitumor activity in 
all types of lymphoma, the Syk inhibitor fostamatinib has activity in diffuse 
large B-cell lymphoma and chronic lymphocytic leukemia, and the PKC-β inhibitor 
enzastaurin is being used as consolidation therapy after remission in diffuse 
large B-cell lymphoma. This review discusses the biology behind the development 
of each new agent and the results of initial clinical trials. The goal is to 
provide the hematologist/oncologist background information on these new agents 
and understand their current and potential role in the management of patients.