title: Phosphodiesterase 4 inhibitors have wide-ranging activity in B-cell malignancies.
abstract: Phosphodiesterase 4 (PDE4) inhibition restores the suppressive effects of 3',5'-cyclic adenosine monophosphate in lymphocytes. In this concise review, we detail how PDE4 inhibition downmodulates the B-cell receptor (BCR)-related kinases spleen tyrosine kinase and phosphatidylinositol 3-kinase and inhibits vascular endothelial growth factor A secretion by tumor cells, inducing cancer cell apoptosis and blocking angiogenesis in the microenvironment. We describe the successful clinical repurposing of PDE4 inhibitors in B-cell malignancies, and propose that given their anti-inflammatory/immunomodulatory activity, these agents will suppress BCR signals without the toxicity associated with other targeted biological doublets.
authors.affiliation: Division of Hematology and Medical Oncology, Department of Medicine.|MD/PhD Program.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Cooney
authors.affiliation: Division of Hematology and Medical Oncology, Department of Medicine.|Cancer Therapy and Research Center, and.|Greehey Children's Cancer Research Institute, University of Texas Health Sciences Center at San Antonio, San Antonio, TX; and.|Audie L. Murphy Memorial VA Hospital, South Texas Veterans Health Care System, San Antonio, TX.
authors.forename: Ricardo C T
authors.initials: RC
authors.lastname: Aguiar
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D000242:Cyclic AMP / Q000378:metabolism; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4 / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000276:immunology*; D058988:Phosphodiesterase 4 Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D058988:Phosphodiesterase 4 Inhibitors; D000242:Cyclic AMP; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4