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

Phosphodiesterase 4 (PDE4) inhibition restores the suppressive effects of cyclic-AMP in lymphocytes. In this concise review, we detail how PDE4 inhibition downmodulates the B-cell receptor (BCR)-related kinases SYK and PI3K, inhibits VEGFA 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.