PGP and neoplasm: As noted earlier, the lower intra-tumor uptake of free ZA compared to NZ [28–32] limits the ability of the former to reduce the synthesis of FPP and ubiquinone, to inhibit the Ras/ERK1/2/HIF-1α/Pgp axis, to impair the energy metabolism, to fully restore doxorubicin's efficacy in vivo.