-PDE5 is overexpressed in numerous cancers-Its inhibition exerts anti-tumor effects through modulating cGMP/PKG signaling; disrupts cancer stem cell maintenance; impairs DNA repair pathways to sensitize cells to chemotherapy; enhances drug uptake via endocytosis; re-programs the tumor microenvironment by blocking pro-tumor inflammatory signals from fibroblasts and MDSCs; and promotes autophagy while inhibiting oncogenic pathways like IL-6/JAK/STAT3. This evidence concerns the gene STAT3 and cancer.