Fasting reverses drug-resistance in hepatocellular carcinoma through p53-dependent metabolic synergism

  title={Fasting reverses drug-resistance in hepatocellular carcinoma through p53-dependent metabolic synergism},
  author={Jelena Krsti{\'c} and Isabel Reinisch and Katharina Schindlmaier and Markus Galhuber and Natascha Berger and Nadja Kupper and Elisabeth Moyschewitz and Martina Auer and Helene Michenthaler and Christoph N{\"o}ssing and Maria R Depaoli and Jeta Ramadani-Muja and Sarah Stryeck and Martin Pichler and Beate Rinner and Alexander J. A. Deutsch and Andreas Reinisch and Tobias Madl and Riccardo Zenezini Chiozzi and Albert J. R. Heck and Meritxell Huch and Roland Malli and Andreas Prokesch},
Cancer cells voraciously consume nutrients to support their growth, exposing a metabolic vulnerability that can be therapeutically exploited. Here we show in hepatocellular carcinoma (HCC) cells, xenografts, and in patient-derived HCC organoids that fasting can synergistically sensitize resistant HCC to sorafenib. Mechanistically, sorafenib acts non-canonically as an inhibitor of mitochondrial respiration, causing resistant cells to depend on glycolysis for survival. Fasting, through reduction… 

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