Eighty per cent of ovarian cancer patients die within the first five years of diagnosis due to recurrence associated with chemoresistance. The proposed study will investigate the role of tissue inhibitors of matrixmetalloproteinases [TIMPs] which regulate extracellular matrix [ECM] remodelling important for metastasis and affect the survival of ovarian tumour cells before and after chemotherapy treatment.
In normal tissues the main role of TIMPs is to inhibit metalloproteinases (such as MMPs, ADAMs and ADAMTS). However in ovarian cancer, before or after chemotherapy, the balance between TIMPs and matrixmetalloproteinases is changed when compared to normal tissues.
We hypothesize that alterations in TIMP signaling are associated with ovarian tumour progression and promote chemoresistance and recurrence in ovarian cancer. The aim of this project is to do a comprehensive analysis of genes and proteins associated with TIMP signalling in primary tumours, chemonaive and recurrent tumours and tumour cells present in ascites fluid obtained from patients with ovarian cancer. This project will also genetically manipulate ovarian cancer cell lines and use in vitro functional assays and mouse xenograft models to better understand the role of TIMP signalling in ovarian cancer progression.
Dr Harry Georgiou (University of Melbourne)