Overview
Topic status: We're looking for students to study this topic.
Our laboratory identified mutations in FGFR2 in endometrial cancer (Pollock et al 2007). Inhibition of FGFR by pan-FGFR small molecule inhibitors leads to inhibition of tumor growth and induction of cell death in vitro and in vivo. Kinase inhibitors have been associated with remarkable clinical responses, however a subset of patients show intrinsic resistance while others often respond initially and then subsequently relapse after developing acquired resistance to these targeted therapies.
Our laboratory has identified an endometrial cell line MFE319 carrying an activating FGFR2 mutation (S252W) that demonstrates intrinsic resistance to FGFR inhibition. To identify the molecules and/or pathway responsible for providing resistance in this cell lines we plan to perform a genome wide siRNA knockdown study.
This project will involve optimizing cell culturing and transfection conditions for this high throughput screen and then performing the screen in conjunction with the Victorian Centre for Functional Genomics at the Peter MacCallum Cancer Centre in Melbourne. One or more of the genes/pathways identified will then be validated by utilizing in vitro and in vivo models to prove that it does indeed provide intrinsic resistance to FGFR inhibition.
- Study level
- PhD
- Supervisors
- QUT
- Organisational unit
Science and Engineering Faculty
- Research area
- Contact
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Please contact the supervisors.
Dr Pamela Pollock
Professor Judith Clements
