Dr Matthew Dun - Funded 2019
PROJECT:
Finding effective treatments for children diagnosed with Diffuse Intrinsic Pontine Glioma (DIPG)
GOAL: To test a never before combined treatment which will help to evaluate safety, efficacy and clinical utility.
Dr Dun's research is focused on finding effective treatments for children diagnosed with diffuse intrinsic pontine glioma (DIPG), a brain cancer diagnosed in younger children whom only survive for 9 months post diagnosis.
DIPG arises in the brain stem, a vital organ that controls breathing and heart rate, as well as the nerves and muscles required for sight, hearing, movement, swallowing and speech. The tumour’s location precludes surgical resection and current chemotherapies do not increase survival. Radiotherapy provides DIPG patients (and their families) with transient benefits, if at all, and therefore this highly aggressive cancer is uniformly fatal.
Our research is focused on finding effective treatments for children diagnosed with diffuse intrinsic pontine glioma (DIPG), a brain cancer diagnosed in younger children whom only survive for 9 months post diagnosis. DIPG arises in the brain stem, a vital organ that controls breathing and heart rate, as well as the nerves and muscles required for sight, hearing, movement, swallowing and speech. The tumour’s location precludes surgical resection and current chemotherapies do not increase survival. Radiotherapy provides DIPG patients (and their families) with transient benefits, if at all, and therefore this highly aggressive cancer is uniformly fatal.
On the 17th of February 2018, Dr Dun’s then two year old daughter, Josephine, was diagnosed with DIPG by Dr Frank Alvaro.
At Josie’s diagnosis, Dr Dun and Dr Alvaro began researching DIPG, established DIPG models in their laboratory. Once established Dr Dun subjected DIPG cells to the type of research that had underpinned his broader cancer research program to-date. Armed with the information identifying the particular genetic mutations Josephine’s tumour harboured, they began investigating the efficacy of a new blood brain barrier permeable, non-toxic drug called ‘GDC-0084’ that had recently completed phase I and phase II clinical trials in the treatment of Glioblastoma multiforme (GBM) - another type of aggressive paediatric and adult brain tumour.
Their laboratory was the first to subject GDC-0084 to rigorous preclinical testing in DIPG. Dr Dun’s laboratory is world renowned for its expertise in protein sequencing or ‘proteomics’ which enables quantitative analysis of a drug’s influence on the physical machinery a cell needs to sustain its growth and survival. By performing high-resolution, quantitative proteomics, or ‘phosphoproteomic profiling’ of DIPG cells treated with GDC-0084, they have revealed mechanisms which drive resistance to therapies that can be targeted with other existing, safe drugs in combination with GDC-0084.
This project will test a never before combined treatment which will help to evaluate safety, efficacy and clinical utility. Dr Dun and Dr Alvaro have exciting laboratory data that needs to be comprehensively tested before we can instigate clinical trials. This is where the Fight on the Beaches funding will go, to fund this testing.
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