Previous studies looking at cyclic AMP levels in brain tumor growth identified the cAMP phosphodiesterase-4 (PDE4) inhibitor Rolipram as a potent antitumor agent Here we specifically look at the role of PDE4 in brain tumors and the potential of PDE4 as a therapeutic agent. Murine brain tumor cell lines (U87,Daoy) were infected with a lentivirus expressing firefly luciferase and either mCherry fluorescent protein alone or the mCherry cassette together with a murine PDE4A1 (mPDE4A1) transgene When PDE4A1 was overexpressed in the tumor cells, in vivo doubling times were significantly shorter compared with controls (Figure 1) In long term survival studies, Rolipram in combination with first-line therapy (chemo- and radiation therapy) enhanced the survival of the mice Bioluminescent imaging indicated that whereas chemo- and radiation therapy arrested intracranial tumor growth, addition of Rolipram resulted in tumor regression (Figure 2).
Goldhoff P, Warrington NM, Limbrick DD Jr, Hope A, Woerner BM, Jackson E, Perry A, Piwnica-Worms D, Rubin JB. Targeted inhibition of cyclic AMP phosphodiesterase-4 promotes brain tumor regression. Clin Cancer Res 2008; 14(23): 7717-25.