Medizinische Universität Graz - Research portal
Selected Publication:
Jagodic, E.
Response of liver cancer-derived cells to starvation in combination with mitochondrial electron transport chain inhibitors
Humanmedizin; [ Diplomarbeit ] Medizinische Universität Graz; 2023. pp. 42
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- Authors Med Uni Graz:
- Advisor:
- Krstic Jelena
- Prokesch Andreas
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- Abstract:
- Liver cell-derived cancers rank third in terms of cancer-associated deaths, and with over 900.000 new cases per year, the sixth most common cancer worldwide. Due to the many different etiologies that lead to the development of the leading variant of liver neoplasm, hepatocellular carcinoma (HCC), the therapy is often very difficult. Depending on the HCC stage, therapy is initiated according to the S3 guideline. If the organ cannot be resected or transplanted by surgery, drug therapy with sorafenib and, in the later stage, regorafenib were for years the only remaining options. Unfortunately, drug therapy frequently can be considered as palliative since resistance development restricts the extension of patient’s life to only a few months. Due to the rewired metabolism resulting from increased growth rate and thus an increased need for nutrients, cancer cells might be more susceptible to fasting. Previous experiments by the Prokesch research group confirmed this assumption, as they found that fasting increases the effects of sorafenib or even sensitizes resistant liver cancer cells to the drug. Mechanistically, sorafenib, primarily used as a multikinase inhibitor, also inhibits the mitochondrial electron transport chain and oxidative phosphorylation (OXPHOS). Our hypothesis was that by suppressing both arms of the rewired metabolism (aerobic glycolysis and oxidative phosphorylation) the growth of HCC cells can be restricted. The goals of this thesis were: (1) to test additional OXPHOS inhibitors in combination with fasting in liver cancer cell lines; (2) to investigate whether glucose is the crucial metabolite whose depletion results in the sensitization to the inhibitor.