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

Jeffrey D. Cooney, Ricardo C.T. Aguiar

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2886-2890
Number of pages5
JournalBlood
Volume128
Issue number25
DOIs
StatePublished - Dec 22 2016

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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