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  Integrative data analysis: from novel biomarker-drug response associations to predicting effective drug combinations

   Centre for Childhood Cancer Research

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  Dr Emmy Dolman, Assoc Prof Paul Ekert  Applications accepted all year round  Competition Funded PhD Project (Students Worldwide)

About the Project

More than 140 children with cancer die in Australia each year due to the occurrence of resistance to traditional chemotherapy. To improve overall survival rates for high-risk paediatric cancer patients, 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 for the generation of patient-derived model systems to link these events to targeted therapies.

WGS, RNA-Seq and DNA methylation profiling of >350 tumour samples showed actionable events in only 70% of the patients. High-throughput drug testing on >150 patient-derived samples yielded unexpected efficacy patterns for single agent targeted drugs without an associated predictive biomarker, but clinical trials for paediatric cancer have proven that treatment with single agents is insufficient in most cases. The current study aims to integrate PRISM molecular profiling and in vitro drug efficacy datasets to identify novel biomarker-drug response associations and predict effective drug combinations for paediatric cancer by developing novel bioinformatic algorithms. Publicly available databases such as DepMap, CancerrXGene and NCI-ALMANAC that contain in vitro efficacy data for single drugs and drug combinations alongside molecular characterisation of the used model systems will be exploited for algorithm optimisation and deeper integrative analysis. Novel discovered biomarker-drug response associations and drug combinations will be validated in vitro and in vivo in patient-derived model systems to guide future clinical trials for paediatric cancer treatment.

Biological Sciences (4) Chemistry (6) Medicine (26)

Funding Notes

Selected applicants will be offered a placement conditional of their success in obtaining a competitive scholarship covering both their living stipend and UNSW Sydney tuition fees as well as receiving an offer of placement in UNSW Sydney faculty of Medicine course code 1825 childhood cancer.