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Project Title: Mixing old treatments with new drugs to cure brain cancer

Grant Amount: $200,000

Institution: Telethon Kids Institute

Investigator Team: Principal investigators A/Prof Nick Gottardo, Dr Raelene Endersby, Prof Terrance Johns and A/Prof Martin Ebert

Grant Type: 2017 Innovation Grant

Years: 2017 - 2020

Brain cancers kill more young people in Australia than any other disease. This project, led by A/Prof Gottardo, focuses on the most common malignant brain cancers of childhood and adulthood, medulloblastoma and glioblastoma respectively. The research project aims to find approaches that enhance existing treatments, prove the new methods work using laboratory techniques, then translate them into clinical trials.

Radiation treatment works by damaging the DNA inside cancer cells, causing the cells to die. However, cancer cells often repair the DNA damage, survive and multiply; leading to treatment failure and cancer regrowth. This project will study two drugs that stop this DNA repair, called iCHK and iATR.

We aim to prove that iCHK and/or iATR enhance the ability of radiation to kill brain cancer cells, without causing damage to the healthy brain.This will lead to new clinical trials, and help achieve more cures and better quality of life for patients.

Highlighted Quote: “This will lead to new clinical trials, and help achieve more cures and better quality of life for patients” - A/Prof Nick Gottardo

Progress: 

First annual progress report (April 2019)

These studies have two important outcomes for children with medulloblastoma. Firstly, we have identified a new combinatorial therapy that appears to enhance radiation-induced G3 MB cell death, and this resulted in significant improvements in survival. These encouraging data require further assessment in additional mouse models of G3MB prior to clinical translation. Secondly, the finding that AZD6738 was not as effective at enhancing radiation-induced G3MB cell death, and the fact that the combinatorial regimen was toxic in animals is equally as noteworthy. 

The rarity of medulloblastoma requires that clinical trials only evaluate the most promising treatments. This is because our patient numbers are few, and maintaining quality of life for patients and their families is imperative. Thus, we are committed to ensuring that the treatments proposed for clinical trial are not only more effective, but also potentially safer for children. This highlights the value or rigorous preclinical assessment of new therapies before considering which ones to take forward to clinical trial. While finding effective therapies is the goal, it is imperative that we also stop ineffective treatments from entering the clinic. 

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