tadalafil + temozolomide

Tadalafil + temozolomide is an investigational combination therapy consisting of tadalafil, a phosphodiesterase 5 (PDE5) inhibitor, and temozolomide, an oral alkylating agent. This combination has been studied in the context of newly diagnosed IDH-wild-type glioblastoma (GBM), where it is administered alongside standard chemoradiotherapy. Tadalafil acts by inhibiting PDE5, leading to increased cyclic guanosine monophosphate (cGMP) levels and vasodilation; it also reduces immunosuppression by targeting myeloid-derived suppressor cells (MDSCs), which are implicated in tumor immune evasion. Temozolomide exerts its antitumor effect through DNA methylation after conversion to its active metabolite MTIC, resulting in DNA damage and apoptosis of rapidly dividing tumor cells. The rationale for combining these agents is that tadalafil may enhance anti-tumor immunity by reducing MDSC-mediated immunosuppression while temozolomide provides cytotoxic activity against tumor cells[1][2][3].