Our results indicate that the simultaneous targeting of tumor cell growth and autophagic cell death by MC‐4 and everolimus results in synergistic antitumor activity mediated by dual inhibition of Akt/PKM2 and mTOR pathways, providing an unexpected opportunity for the development and implementation of drugs targeting cell metabolism and aberrant Akt/PKM2 signaling. The gene discussed is AKT1; the disease is neoplasm.