Aberrant cancer metabolism has been recognized to be an attractive target for cancer treatments. However, inhibition of a single metabolic pathway has limited efficacy. In this study, a strategy to con-currently inhibit tumor glycolysis and oxidative phosphorylation is proposed. An antiglycolytic drug and artificially synthesized mitochondria-targeting polypeptide were simultaneously applied to com-pletely deplete the energy source of cancer cells, eventually leading to a synergetic effect of cancer star-vation therapy. In vitro results show the mechanism and evidence of the cooperative effect of this combinatorial approach. This study is expected to provide new perspectives of cancer starvation treat-ments by inhibiting various metabolic pathways. (c) 2021 The Korean Society of Industrial and Engineering Chemistry. Published by Elsevier B.V. All rights reserved.