Overview
Topic status: We're looking for students to study this topic.
The family of fibroblast growth factor (FGF) signalling molecules is complex with multiple FGF ligands and receptors. Our laboratory identified mutations in FGFR2 in endometrial cancer (Pollock et al 2007). Members of the FGFR family are also activated in other tumour types including breast and gastric cancer and multiple myeloma. Inhibition of FGFR by pan-FGFR small molecule inhibitors leads to inhibition of tumour growth and induction of cell death in vitro and in vivo. Multiple FGFR inhibitors are currently in preclinical development and clinical trials. Kinase inhibitors have been associated with remarkable clinical responses, however often patients subsequently relapse and develop resistance to these targeted therapies. Our lab is currently investigating mutations identified in a BaF3 screen for Dovotinib resistance to determine if they can provide resistance to different clinical relevant FGFR inhibitors (eg E7080, BIBF1120) and thus provide insight into the design of second generation inhibitors. By culturing in slowly increasing concentrations of Dovotinib our laboratory has also generated both breast and endometrial cancer isogenic cell lines that are now resistant to Dovotinib, currently in multiple clinical trials. These cell lines will be characterized using a wide variety of technologies to identify the mechanisms of resistance.
Hypothesis: Resistance to FGFR inhibitors can be provided by mutation in the kinase domain or the activation of parallel or downstream signalling pathways where the latter is likely to be different in different in different cell types.
Methods and techniques that will be developed in the course of this project:
- Cell and molecular Biology, intracellular signalling
- Translational cancer cell biology
- Phosphoproteomics, Next Generation transcriptional sequencing, siRNA kinome knockdown
- Study level
- PhD
- Supervisors
- QUT
- Organisational unit
Science and Engineering Faculty
- Research area
- Contact
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Please contact the supervisor.
Dr Pamela Pollock
Professor Judith Clements
