Impact of ketogenic diet on tumor behavior (ESR 11)

 

 Project Description

 

1) Job description: At the Department of Paediatrics at the Paracelsus Medical University in Salzburg – Austria an early stage researcher (ESR) position is available. We are a multi-disciplinary centre of competence whose objective is to offer diagnostic services and research for mitochondrial disorders. Based on our extensive competence in mitochondrial biology we also established a research program on tumor metabolism

The gold standard in cancer therapy is still based on surgery, chemotherapy and radiation therapy. Although major advances were achieved in recent years, cancer therapy has still a range of severe side effects and limited success in certain types. Although, tumours show an enormous biological heterogeneity the majority shares one remarkable and fundamental feature, which is a switch from OXPHOS to glycolysis/Warburg effect. Even if sufficient oxygen for respiration is present, tumor cells prefer glycolysis for energy production and down-regulate OXPHOS. Recently it has been demonstrated that by means of a ketogenic diet (KD) it is possible to target the increased glucose dependence of cancer cells. Data generated by our group show that a classical high- fat low- carbohydrate diet is able to significantly decelerate growth of neuroblastoma xenografts (PMID: 26053068). To date it is unclear if the effect of KD on tumor growth is solely due to reduction of blood glucose levels. KD induces changes in body hormone levels, which is a mechanism explaining the effectiveness of KD in the treatment of certain types of epilepsy. Furthermore, recent data indicate that ketone bodies generated upon degradation of fatty acids have direct anti-proliferative effects. To elucidate if KD exerts its effect on tumour growth dependent on the status of aerobic energy production we will treat xenografts of glycolytic and oxygenic tumors with KD. Furthermore, we will test the influence of KD on the growth of tumors with differences in chemoresistance and will elucidate if KD can influence cancer metastasis. The ESR will analyze the effect of KD on xenografts regarding markers of proliferation, apoptosis as well as cancer stem cells. The studies will reveal if the success of the dietary intervention depends on specific alterations of tumor cell metabolism.

Principal Investigator: Prof. Barbara Kofler

ESR 11: Daniela Weber

 

Key personnel:

Dr. René Feichtinger, Post-Doc fellow

Sepideh Aminazdeh Gohari, PhD fellow

Prof. Johannes Mayr