Ovarian cancer is the 5th most common cancer in women in Western countries. A major clinical problem is the development of acquired chemoresistance, resulting in a 5-year survival rate of only 30%. There have been numerous studies investigating acquired chemoresistance in vitro, however they are limited due to the induction of resistance in cancer cell lines rather than examining clinically induced resistance. As part of my Masters project I will be investigating two patients obtained from the Australian Ovarian Cancer Study. These studies explicitly involve comparison of ovarian tumour tissue collected at primary surgery with patient-matched relapse samples. Women were initially sensitive to chemotherapy but acquired resistance.
Using high-resolution genome wide DNA copy number change (CNC) analysis we aim to identify key mechanisms associated with acquired chemoresistance. Preliminary analysis has identified a number of regions uniquely amplified in the relapse resistant sample compared with its matched primary sensitive sample. I aim to identify whether these are new events arising during disease progression or whether they are pre-existing in the primary tumour in a small cell population that is selected and expanded during chemotherapy treatment. To achieve this I am further analysing these regions in series of tumour samples collected from these patients over the course of disease progression, using a combination of copy number and gene expression analysis.
Additionally, our lab has established a number of ovarian cancer cell lines from patients where detailed clinical data is available, including the two patients in the above study. These cell lines will allow us to functionally explore the effect of identified genes on drug resistance and tumour progression. These studies will have implications for the treatment of acquired resistant ovarian cancer and may indicate pathways that may be subjected to early intervention to restore sensitivity.