Biological modelling of FGFR1-altered paediatric cancers to identify effective therapeutic strategies

Genomic analysis of over 400 paediatric cancer patients (by the Zero Childhood Cancer Program) has identified the recurrence of alterations, including single nucleotide variants, gene fusions, and intragenic deletions affecting the fibroblast growth factor receptor 1 (FGFR1) gene in a range of cancer types. FGFR1 encodes a receptor tyrosine kinase, which when activated in cancer typically results in activation of intracellular signalling pathways, including PI3K/AKT and RAS/MAPK, driving cell proliferation and survival. FGFR1 may be therapeutically targetable with tyrosine kinase inhibitors but further understanding of how specific variants drive cancer is needed to implement these therapies clinically.

This project aims to develop and use biological models to understand the mechanisms by which FGFR1 oncoproteins drive cancer and identify rational therapies to treat patients with FGFR1-altered cancers.

The student would perform functional validation of a novel FGFR1 fusion gene using a range of molecular and cell biology techniques including cell culture, viral transfection/transduction, flow cytometry, western blotting, cell viability and proliferation assays, and drug treatment assays. This work will be extended to include analysis of a broader range of FGFR1 variants to identify signalling mechanisms and drug susceptibilities that are common and unique to different FGFR1 variant classes. In addition to the techniques described above, the candidate will use unbiased screening methods including phosphoproteomics and high-throughput drug screening.