TY - JOUR
T1 - Phosphodiesterase 4 inhibitors have wide-ranging activity in B-cell malignancies
AU - Cooney, Jeffrey D.
AU - Aguiar, Ricardo C.T.
N1 - Funding Information:
J.D.C. was supported by the National Institutes of Health, National Cancer Institute (1F30CA206343-01). R.C.T.A. was supported in part by an award from the Cancer Prevention and Research Institute of Texas (CPRIT; RP15077), the Owens' Foundation, and the Leukemia and Lymphoma Society (TRP-6524).
Publisher Copyright:
© 2016, American Society of Hematology. All rights reserved.
PY - 2016/12/22
Y1 - 2016/12/22
N2 - 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.
AB - 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.
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U2 - 10.1182/blood-2016-09-737676
DO - 10.1182/blood-2016-09-737676
M3 - Article
C2 - 27756749
AN - SCOPUS:85014883012
VL - 128
SP - 2886
EP - 2890
JO - Blood
JF - Blood
SN - 0006-4971
IS - 25
ER -