Research in the Women’s Oncology Unit can be broadly divided into clinical research and laboratory based research with the former usually under the aegis of the Australia & New Zealand Gynaecology Oncology Trials Group (ANZGOG) and the latter in the laboratories at the Women’s Cancer Research Centre.
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Clinical Research
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Most of the clinical research trials revolve around ovarian cancer and fall into two broad categories. The first is the trials of new agents, which are usually brought to our trials groups by pharmaceutical companies. The second category are “Phase III” trials in which new treatments are compared with the current gold standard, which for ovarian cancer is a combination of carboplatin and taxane chemotherapy.
Most of the Phase III trials involve the use of new agents, either as first line treatment following surgery or alternatively when cancers relapse, comparing new agents with standard “second line treatments” is then undertaken.
Other clinical trials that we are involved in apart from ovarian cancer include a trial of laparoscopic surgery compared with standard surgery in patients with endometrial cancers, and intraperitoneal therapy – that is chemotherapy that is given directly into the abdominal cavity rather than directly into a vein.
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Laboratory Research
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Bridging the gap between the laboratory and the bedside are two studies, the first in ovarian cancer and the second cancer of the lining of the womb (“endometrium”) in which patients have been interviewed about their past medical, surgical, family and medication histories and the tumour is sent for genetic analysis to try and correlate changes in the tumour gene profile with the patient’s own personal history. Both of these studies are very large studies involving more than 1,000 patients, currently being undertaken in trials supported by the NHMRC.
Other important clinical investigations have included the follow up study looking at pregnancy outcomes in women who have undergone treatment for cervical dysplasia which has suggested that laser treatment, rather than excisional treatments of precancerous changes, gives better outcomes. This has led us to institute a large international cooperative study to examine this further.
Also bridging the laboratory and bedside is a study looking at the immune system in women with cancers. We have noted that there seems to be a cycling of the immune system occurring every 7-10 days, and this cycle may be a useful tool in which to administer low dose chemotherapy in the hope that the body’s own immune defences will kill off the cancer cells rather than having to rely on cytotoxic chemotherapy drugs.
Our laboratory research is studying how ovarian cancers become resistant to chemotherapy. The team is identifying genes that are activated and deactivated in cells taken from the primary (early) tumour, which are sensitive to chemotherapy, and also genes that are activated and deactivated in chemoresistant cancer cells from the same patient. Comparing samples from the same patient is a critical point as the only differences between the two tumour samples should be entirely due to the development of resistance to chemotherapy.
It is hoped that characterizing how cisplatin and paclitaxel influence gene activation and deactivation will identify gene targets for new therapeutic strategies that can prevent or circumvent ovarian cancer from becoming resistant to chemotherapy.
We are also looking at the way ovarian cancer spreads using a unique laboratory model which has been developed to allow us to examine important molecules which may be responsible for the detachment of cancer cells and their eventual implantation in secondary sites.
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