Sydney West Translational Cancer Research Centre
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Drs Eric Hau & Han Shen: Overcoming Treatment resistance in Brain Tumours with Metabolic Modulation

Children’s Cancer Research Unit (CCRU) Seminar



Oncology Conference Room, CHW

Because radiation therapy significantly increases median survival in patients with gliomas, the modulation of radiation resistance is of significant interest. High glycolytic states of tumour cells (the Warburg effect) is a metabolic hallmark of most cancer cells and are known to correlate strongly with radiation resistance; thus, the concept of metabolic targeting needs to be investigated in combination with radiotherapy. Dichloroacetate (DCA), a pyruvate dehydrogenase kinase (PDK) inhibitor currently being used to treat lactic acidosis, can modify tumour metabolism by activating mitochondrial activity to force glycolytic tumour cells into oxidative phosphorylation. Out study demonstrated that by reversing the Warburg effect, DCA significantly enhanced the anti-tumour effects of radiation in both in vitro and in vivo models of adult glioblastoma (GBM) and paediatric diffuse intrinsic pontine gliomas (DIPG). This radiosensitising effect was further improved when multiple metabolic pathways were concurrently blocked therapeutically. Our findings suggest modulating aberrant glucose metabolism is an effective therapeutic approach to target cancer cells and improve the efficacy of radiation therapy.

About the speakers: Dr Eric Hau is a radiation oncologist at Westmead, Blacktown and Nepean Hospitals. He completed his PhD at the Lowy Cancer Research Centre on pre-clinical radiation/drug testing and now leads the Translational Radiation Biology and Cancer Research Group at Westmead Institute of Medical Research. He is also an active clinical trialist.

Dr Han Shen completed his PhD degree at UNSW Sydney on the role of aberrant glucose metabolism in the treatment of malignant brain tumours in 2014. He then worked as a postdoctoral scientist on pre-clinical testing of glucose metabolism inhibitors as a therapeutic strategy to improve the radiosensitivity of tumour cells. Dr Shen joined Children’s Cancer Institute in 2015 to investigate the novel therapeutics for DIPG. Dr Shen joined Dr Eric Hau’s laboratory in 2017 investigating the novel radiosensitising therapeutic strategies against malignant brain tumours and melanoma.