Poster Presentation 36th Lorne Cancer Conference 2024

Paediatric Oncology Revolution: Unleashing Precision Medicine through Phosphoproteomics (#127)

Terry Lim 1 2 3 4 , Paul Daniel 4 , Claire Sun 4 , Nicole Chew 4 , Dilru Habarakada 4 , Roger Daly 1 , Ralf Schittenhelm 1 3 , Ron Firestein 4 , Pouya Faridi 1 2 3 4
  1. Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia
  2. School of Clinical Sciences, Department of Medicine, Monash University, Clayton, VIC, Australia
  3. Monash Proteomics and Metabolomics Platform, Department of Biochemistry and Molecular Biology, Monash Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia
  4. Hudson Institute of Medical Research, Clayton, VIC, Australia

The battleground against childhood cancer is an ongoing struggle, where each child's unique genetic makeup and tumour profile present a complex puzzle. Emerging technologies and cutting-edge techniques, such as phosphoproteomics and other multi-omics approaches, have set the stage for a transformative paradigm shift in the field of paediatric oncology. More importantly, phosphoproteomics has enable the profiling of aberrant kinases, which are critical enzyme found to be often dysregulated in cancer. In this project, we delve into the captivating world of phosphoproteomics, unlocking their potential to guide the way towards brighter, more hopeful futures for childhood cancer.

In this study, we present a robust mass spectrometry-based phosphoproteomics methodology aimed at profiling a growing cohort of paediatric cancer patients. Notably, this undertaking represents one of the most comprehensive investigations into phosphoproteomics that is specifically tailored for paediatric cancer. Our analysis encompasses an extensive dataset, comprising of over 140 samples derived from more than 15 paediatric cancer subtypes, including medulloblastoma, osteosarcoma, atypical teratoid rhabdoid tumour (ATRT) and one of the most devastating brainstem tumours, diffuse midline glioma (DMG). Through our rigorous examination, we are able to monitor the protein and phosphorylation changes of more than 10,000 proteins and in excess of 21,000 distinct phosphosites across these samples.

Ultimately, we want to integrate this wealth of data with other extensive multi-omics datasets generated within the group. These include datasets stemming from RNA sequencing, CRISPR knockout (KO) screening, and drug screening initiatives. By harnessing the integrative potential of this multifaceted information, our aim is to predict actionable molecular targets, in the hope of facilitating the development of highly individualised and efficacious therapeutic strategies, such as drug repurposing and immunotherapy, for paediatric cancer patients. This scientific pursuit holds immense promise for enhancing the prospects of improved, personalised care for paediatric oncology.