John Turner Professorial Cancer Research Fellow, Professor Nuzhat Ahmed, Dr Elif Kadife, University of Melbourne PhD candidate Ruth M Escalona and Professor George Kannourakis have identified a new potential strategy
to overcome chemoresistance-associated in ovarian cancer patients who do not have many treatment options. This recent research paper “TIMP-2 regulates proliferation, invasion and STAT3-mediated cancer stem cell-dependent chemoresistance in ovarian cancer cells” has been published in international science journal-BMC Cancer.
This research was completed in collaboration with Ovarian cancer team at the Centre for Reproductive Health at the Hudson Institute of Medical Research.
Over 1500 women are diagnosed with ovarian cancer in Australia each year. Due to late diagnoses this is a difficult cancer to treat. The cancer histologically and genetically is very complex causing significant impediments in effectively treating patients. Standard treatment of patients consists of surgery, followed by chemotherapy, which in most cases unfortunately can end in recurrent chemo resistant disease.
80% of patients die within five-years of diagnosis due to chemoresistance-associated recurrence.
The manuscript shows that a protein, tissue inhibitor of metalloproteases-2 (TIMP-2), involved with the remodelling of ovarian tissues during normal physiological processes, is highly expressed in advanced-stage ovarian tumours. Knock down of this protein (TIMP-2) in ovarian cancer cells makes the cells sensitive to chemotherapies, which are currently used for ovarian cancer patients. The manuscript also shows that high expression of TIMP-2 is essential for maintaining the activation of a signalling pathway (STAT3) necessary for tumour growth, dissemination and chemoresistance. Knock down of TIMP-2 expression hinders the activation of STAT3 absolutely essential for chemo resistant mechanisms. The above novel finding suggests that manipulation of TIMP-2 expression in ovarian cancer cells may provide a new strategy to overcome chemoresistance-associated in ovarian cancer patients who do not have many treatment options.