Signal transduction inhibitor therapy for lymphoma.
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.
Division of Hematology, Department of Internal Medicine, Mayo Clinic College of Medicine and Mayo Foundation, Rochester, MN 55905, USA. witzig@mayo.edu
Thomas E
TE
Witzig
Mamta
M
Gupta
D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D008223:Lymphoma / Q000188:drug therapy* / Q000201:enzymology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011947:Receptors, Antigen, B-Cell; D058570:TOR Serine-Threonine Kinases
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