Victorian researchers have discovered a protein that could play a key role in switching off resistance to chemotherapy in ovarian cancer.
For many ovarian cancer patients, treatment stops working when the cancer become resistant to chemotherapy and the high mortality rate of ovarian cancer - with 60 per cent of patients dying within five years of diagnosis - is due to this chemoresistance.
Researchers at the Fiona Elsey Cancer Research Institute in Ballarat have found for the first time that some proteins can be used as targets to prevent disease progression and "switch off" chemoresistance.
The finding is significant because there are no treatment options for chemo-resistant ovarian cancer patients and could potentially prolong the lives of patients with advanced disease.
Publication of the research in the Frontiers in Oncology journal comes just weeks after the Ballarat community again showed its strong support for FECRI coming out in force for the institute's two major fundraisers Ballarat Cycle Classic and Begonia Classic which raise funds for cancer research projects such as this one.
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As Australia's only regionally based cancer research centre, FECRI relies on community fundraising and donations to continue their cancer research and potentially change the outcomes for people diagnosed with cancer.
FECRI director Professor George Kannourakis said their latest discovery was "potentially a new strategy to target chemo-resistant ovarian cancer cells".
"We discovered a new mechanism that wasn't detected before that seems to be switched on in ovarian cancer cells that are no longer responsive to chemo," Professor Kannourakis said.
The proteins involved in this mechanism of resistance are known as metalloproteinases (MMPs) and their inhibitors (TIMPs).
They found TIMPs were low when ovarian cancer cells did not respond to chemotherapy.
"We can try to find a way of increasing or altering the balance between the two, and it may be possible to use a pharmacological way of doing that so we can increase more of the TIMPs in the cell to respond to chemotherapy better," he said.
This study, conducted by PhD candidate Ruth Escalona, supervised by Professor Nuzhat Ahmed and involving Professor Kannourakis, is the first to analyse this mechanism in ovarian cancer patient samples before and after chemotherapy treatment.
"The mortality rate of ovarian cancer is high ... as most ovarian cancer presents as advanced disease that has already spread throughout the peritoneal cavity, which is stage three ovarian cancer, and sometimes it can go to other organs and that's stage four.
"When it presents as advanced disease ... only about 40 per cent of people survive five years with chemotherapy and all the treatments we have ... so 60 per cent die within five years.
"Unfortunately once you get a recurrence and chemo is no longer working, it is a chemo-resistant disease most people don't survive very long, so finding a positive pathway to act on we may be able to alter that so we can make these resistant cells responsive again to chemotherapy and potentially prolong the lives of patients with advanced disease."
The research project has been running for more than four years and being carried out in conjunction with a laboratory in Melbourne.
"Anything in ovarian cancer that you can find - an achilles heel for chemo-resistant cells - is a good thing," Professor Kannourakis said.
More than 1040 women died of ovarian cancer in Australia last year, with ovarian cancer making up five per cent of new cancers diagnosed in women.
There are no early detection screening tests and often the symptoms of ovarian cancer are missed or mistaken for other common complaints. Lack of early detection and chemo resistance make t a difficult cancer to treat.
Professor Kannourakis said more work was needed to determine whether their finding could be a clinical solution to potentially target cancer cells.
"Maybe we'll be able to switch the bad enzyme off and put the good enzyme in to let the cells respond. If we can find a way to alter (the levels), if there are medications around that could do that, the next trial is to do in-vivo testing of whether we can grow ovarian cancer from humans in to mice to allow us to see whether we can inhibit the process."
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