In the same study, PDE5 inhibitors (e.g., sildenafil and tadalafil) were shown to synergize with COX-2 inhibitors in blocking tumor growth through activation of CD95 death receptor/JNK and the subsequent induction of autophagy, endoplasmic reticulum stress signaling, suppression of sphingosine-1- phosphate (S1P) signaling and ceramide synthesis, as well as by deregulating several signaling pathways linked to cell proliferation (MAPK/ERK, Akt, mTOR, NFκB). Here, PDE5A is linked to neoplasm.