PDE5A and neoplasm: Therefore, combination therapy of advanced cancers should necessarily include anti-inflammatory therapy conducive to “cooling down” exaggerated tumor-mediated inflammation and to dampen pro-tumor immune activity [17] by drugs such as cyclooxygenase-2 (COX-2) inhibitors, H2-blockers, phosphodiesterase-5 (PDE-5) inhibitors, statins, activator of AMP-activated protein kinase, and glucocorticoids [4,16].