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Explaining unexplained drug responses in childhood sarcomas


   Centre for Childhood Cancer Research

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  Dr Emmy Fleuren, Dr Ashleigh Fordham  Applications accepted all year round  Competition Funded PhD Project (Students Worldwide)

About the Project

Despite aggressive treatments, survival of young, high-risk sarcoma patients is poor and side-effects are frequent. No targeted treatment is available, underlining the unmet need for better and less toxic treatments. Finding better treatments is however challenging.

The ZERO Childhood Cancer Program (ZERO) is Australia’s first-ever personalised medicine program for children with high-risk cancer, including sarcomas. ZERO’s comprehensive testing platform is unique, as it includes not only whole genome, RNA and methylation profiling, but also functional in vitro and in vivo testing.

In this project, the student will address a major clinical challenge in ZERO: explain unexplained drug responses observed when we exposed high-risk paediatric sarcoma patient samples to 125 different anti-cancer drugs.

Excitingly, drug responses were observed in 60% of sarcoma patients. In at least 8 patients, we have however no idea why these patient’s tumours respond so well. These unexplained drug responses turned out to be a major clinical-translational bottleneck: when we do not know why a drug is so effective in vitro, this drug is usually not recommended to the patient.

The student will use various molecular methodologies, including Mass-Spectrometry and targeted phosphoproteomic assays (Kinome Profiler/Western Blot/Immunohistochemistry) to investigate target activation patterns, and correlate this with genomics and transciptomics patient data. In vitro siRNA and drug assays will be employed for functional validations. Broader kinome-siRNA/CRISPR screens (+/- drug) will be added, plus in vivo drug inhibition studies later in the project.

The ultimate aim is to generate the evidence needed to transform drug findings into actual clinical recommendations.

References

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All students at the Institute must fulfil the requirements for enrolment at UNSW to undertake their PhD with us as well as obtain a scholarship that will cover both your living expenses and tuition fees. Scholarship and entry requirements will be provided on request.
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