Phosphodiesterase 4 inhibitors have wide-ranging activity in B-cell malignancies.

Jeffrey D Cooney, Ricardo C T Aguiar

Blood 2016 Dec 22

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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.

Citation

Jeffrey D Cooney, Ricardo C T Aguiar. Phosphodiesterase 4 inhibitors have wide-ranging activity in B-cell malignancies. Blood. 2016 Dec 22;128(25):2886-2890