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Tailored PROTACs to target the undruggable in paediatric cancer

   Centre for Childhood Cancer Research

  ,  Applications accepted all year round  Competition Funded PhD Project (Students Worldwide)

About the Project

Around 200 children are diagnosed with high-risk cancer in Australia each year. Over 140 of these children still die due to the occurrence of resistance to traditional chemotherapy. To improve overall survival rates for high-risk paediatric cancer patients, treatment developments have been shifted to personalised approaches. To achieve this aim, the Children’s Cancer Institute initiated the Zero Childhood Cancer national personalised medicine trial (PRISM). Within this trial, tumour biopsies from children with high-risk cancer are collected for full molecular profiling to identify cancer driver events and the generation of patient-derived model systems to link these events to targeted therapies.
Results so far showed that 70% of the patients harbour events in genes that can be hit by clinically available or investigated drugs. However, drug effects in some cases do not cover all oncogenic functions associated with the aberrated gene (e.g. EZH2) or, alternatively, can be circumvented by allosteric effects of other proteins (e.g. CDK4). In addition, there are still numerous driver events in paediatric cancer for which no drug is available (e.g. transcription factor fusion genes). The current project aims to target incompletely drugged or undruggable cancer drivers identified in high-risk paediatric cancer patients by developing tailored proteolysis-targeting chimeras (PROTACs). Instead of target inhibition, bifunctional PROTACs cause ubiquitination-mediated proteasomal degradation by recruiting E3 ligases to the targets of interest. PROTACs are associated with more potent and longer lasting effects compared to conventionally studied small-molecule drugs and open new avenues for improved paediatric cancer treatment.
To help us determine your suitability for postgraduate studies with us could you please send through a copy of your full academic transcript.

Funding Notes

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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