Revati Sharma

Supervisors: Professor Nuzhat Ahmed, Dr Prashanth Prithviraj and Professor George Kannourakis
School of Health and Life Sciences, Fiona Elsey Cancer Research Institute, Ballarat
revatisharma@students.federation.edu.au
Doctor of Philosophy

"Epithelial-to-Mesenchymal Transition and cancer stem cells: Robust biomarkers in Renal Cell Carcinoma”

Background: Epithelial-to-Mesenchymal Transition (EMT) and cancer stem cells (CSC) have been shown to be requisites for cancer metastasis and therapy resistance in RCC. There has been accumulating evidence suggesting that the potential reason behind the failure of conventional therapy failure is because the cancer cells have phenotypically changed themselves into CSCs using EMT programme. This activation of EMT further confers the tumour cells resistance to many therapeutic agents including sunitinib. The identification of new biomarkers and druggable targets will be thus be of great clinical importance in RCC.

Hypothesis and Aims: We hypothesise that RCC tissues inherently express signatures of EMT and CSC pathways. We also hypothesise that both EMT and CSCs are critical regulators of sunitinib resistance in RCC cells. Hence, targeting the EMT or CSC modulating pathways in combination with sunitinib may re-sensitise RCC to Sunitinib treatment.

Methods and Results: In this study, we demonstrate RCC tissues display signatures of EMT and CSCs. We also show that RCC cell lines resistant to sunitinib have enhanced expression of EMT and CSC markers.

Conclusion: EMT, as a mechanism of intrinsic or acquired resistance to targeted therapy has the potential to be a robust predictive and prognostic marker in patients with RCC.

Revati Sharma is supported by an Australian Government Research Training Program (RTP) Fee-Offset Scholarship
through Federation University. Revati is also supported by John Turner PhD Scholarship