RDX and cancer: The present study provides a first molecular clue to (H-1)PV oncoselectivity: on the one hand, growth-factor- and PI3K-independent activation of PDK1/(PKB) signaling may contribute to cancer progression in an unfavorable environment; on the other hand, the newly identified PKCη/Rdx-driven loop-back activation of PDK1 induced by PVs in cancer cells, but not in normal cells, appears to favor PV amplification and cytotoxicity and to counteract virus-induced stress responses.