In the early stages of ovarian cancer many women have no symptoms, hence its ominous name as the 'silent killer'. If symptoms do appear, they are vague and include swelling and pain in the abdomen; changes in the usual menstrual pattern, or postmenopausal bleeding; gastrointestinal symptoms such as heartburn, nausea and bloating; changes in bowel habits, such as constipation and diarrhoea; tiredness and appetite loss; and unexplained weight loss or weight gain. Because these symptoms can be common in healthy women, particularly women who are going through menopause, ovarian cancer is often not diagnosed until it is more advanced, making it more difficult to treat. Unlike other major female cancers such as breast and cervical cancer, there is currently no screening test for early signs of ovarian cancer. The Pap smear test does not detect ovarian cancer.

Most ovarian cancers occur sporadically, that is, they are not associated with any known hereditary factors. However, around 5-10% of ovarian cancers are caused by inheriting a damaged gene. Most hereditary ovarian cancers are associated with the BRCA1 or BRCA2 genes, also associated with familial breast cancers. A small number of hereditary ovarian cancers are associated with a particular type of familial colorectal (bowel) cancer.

Other risk factors for ovarian cancer include a high number of ovulatory cycles. Women who ovulate less over their lifetime are somewhat protected from developing ovarian cancer. Therefore, having few or no children, having a first child after the age of 30, and having early commencement of menstruation or late menopause increases your risk of developing ovarian cancer. The long-term use of a combined oral contraceptive pill and breastfeeding, both of which suspend ovulation, lowers the risk of developing ovarian cancer.

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Ovarian cancer is normally diagnosed by a gynaecological oncologist. Tests commonly used to aid its diagnosis include: a physical examination of the abdomen to look for swelling; a transvaginal ultrasound to create an image of the ovaries; and the CA125 blood test. CA125 is a substance produced by some ovarian cancer cells and by some normal tissues. A high CA125 level can indicate ovarian cancer or a benign (non-cancerous) gynaecological condition. Hence, the CA125 test is not used alone to diagnose ovarian cancer. Surgery and subsequent pathological examination of the ovaries are the only definitive way to diagnose ovarian cancer.

The type of treatment depends on the age of the woman, the type of ovarian cancer, and its stage of progress. The most common treatment method is an individualised combination of surgery and chemotherapy. During surgery, either a portion of the ovary or the entire ovary may be removed. If the cancer has spread to surrounding areas, most commonly surrounding organs in the abdominal cavity, surgical removal of cancerous tissue from other affected organs may also be required. After surgery, chemotherapy is used to kill any remaining cancer cells. Currently, the most common type of chemotherapy for ovarian cancer patients is a combination of carboplatinum and paclitaxel.

Unfortunately, there is a lack of effective therapies for advanced disease, particularly for women who develop resistance to standard chemotherapy approaches. Hence, early detection tests and new treatments are vital if we are to improve the survival for women diagnosed with ovarian cancer.

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Our work revolves around identifying the genes that cause the development of ovarian cancer, and using this information to identify new ways of diagnosing and treating ovarian cancer. We rely on a close collaboration with the Gynaecological Cancer Centre at the Royal Hospital for Women in Sydney, one of NSW’s major treatment centres for women with ovarian cancer. Comprehensive clinical information, tissue, and blood samples are collected from patients who are being treated for ovarian cancer.

Using genomic approaches that allow the screening of all human genes at one time, we have identified many genetic changes that may be involved in the development of ovarian cancer.  For example, using gene expression profiling, a powerful screening approach that identifies which genes are turned on or off in ovarian cancer compared to normal ovarian epithelial cells, we have shown that the different types of epithelial ovarian cancer are genetically distinct. The mucinous type of ovarian cancer, in particular, stands out from the others.  Together with results from other groups around the world, this information has led to new clinical trials that are testing different types of chemotherapy for women with the mucinous type of ovarian cancer.

Although relatively rare, mucinous ovarian cancer is often confused with metastases from the gastrointestinal (GI) tract. As ovarian and GI cancers may have widely different outcomes and are treated with different types of chemotherapy, it is vital to make the correct diagnosis. To this end, we also have identified new markers that can distinguish mucinous ovarian cancer from GI cancers that have spread to the ovary, which will aid in ensuring that patients receive the most appropriate treatment for their cancer.

We have also identified markers that may lead to new treatment options for women with ovarian cancer. For example, we have shown that women whose cancers produce high levels of a marker called EDD are twice as likely to succumb to their cancer than those with low levels. Our research shows that this is likely due to EDD mediating the development of resistance to chemotherapy treatment, one of the major causes of the poor survival for women with ovarian cancer. These results suggest that new treatments based around EDD may be useful for women who develop chemoresistant disease.

Our major focus remains to identify better ways of diagnosing early stage ovarian cancer, preferably as a simple blood-based test. Tumour suppressor genes are critical for preventing unrestrained growth of cells, and their switching off is one of the key and early events in development of cancer. These genes are often silenced by an epigenetic modification to their DNA called methylation. Preliminary evidence from our group and others suggests that such DNA methylation changes may be detectable in the blood of patients with early stage ovarian cancer. We have now discovered a number of candidate tumour suppressor genes that are silenced in ovarian cancer by methylation and that are detectable in blood samples from ovarian cancer patients. Our current work focuses on identifying a panel of these methylated markers that may have potential as diagnostic markers for early stage ovarian cancer.

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