University of Queensland researchers have discovered a way to block the growth of kidney cancer tumours.
Their research may lead to the development of an effective systemic therapy of renal cell carcinoma or kidney cancer, which cannot be treated by other cancer therapies.
About one in every 800 Australians develops kidney cancer, which accounts for about two percent of all malignancies as well as two percent of all cancer deaths.
The researchers are now planning to determine whether the inhibition of a growth factor found in kidney cancer will prevent further growth of these existing tumours.
The team, based at the Princess Alexandra Hospital, has also discovered that a drug used to treat hypertension inhibits the growth of kidney tumours.
PhD student Su-Ing Hii has been studying renal cell carcinoma for the past two years under the supervision of urologist Dr David Nicol and surgeon Dr David Gotley, both from the University's Surgery Department.
Mrs Hii examined a recently defined tumour growth factor in renal cell carcinoma called vascular endothelial growth factor (VEGF).
VEGF is the critical factor for kidney cancer angiogenesis (the formation of new blood vessels from pre-existing blood vessels) and essential to growth and progression of these tumours.
'Inhibition of angiogenesis may be a potential anti-cancer therapy and treatment with angiogenesis inhibitors has proven anti-tumour effects in animals,' Mrs Hii said.
'At present kidney cancer can be treated only with surgery and the management of patients with advanced kidney cancer is a major problem.
'Patients usually present with symptoms such as back pain and blood in the urine, and by the time of diagnosis, the tumour has already spread in about 30 percent of patients to other organs, particularly to the lungs and bones.
'Once the tumour spreads it's almost untreatable and most patients die within 12 months.
'We need a new treatment which can be developed by analysing the underlying mechanism of kidney cancer growth and determining how these may be manipulated.'
For her PhD, Mrs Hii took samples of healthy kidney tissue and kidney tumour tissue from 25 patients.
A comparison of both samples found higher levels of VEGF in tumour tissue compared to normal tissue.
'Once the tumour reaches the size equivalent to a green pea, VEGF signals other growth factors to break down the outer cells of the blood vessel. These outer cells then form blood vessels and feed back into the tumour,' Mrs Hii said.
'The tumour can then grow bigger because it has its own blood supply, instead of living by diffusion alone.
'The way VEGF facilitates tumour development suggests that if VEGF could be controlled, we could also regulate tumour development.'
To inhibit the expression of VEGF at the molecular level, Mrs Hii used an antisense strategy on young rats, which involved preventing a strand of DNA translating into protein needed for VEGF expression or angiogenesis.
Mrs Hii is now developing and testing monoclonal antibodies to VEGF to test the activity of antibodies in adult mice with kidney tumours.
For her research, Mrs Hii has also compared the results of an anti-hypertensive drug Captopril on adult mice with tumours.
After six weeks of treatment, she found a significant dose-related reduction in tumour development compared to mice that did not receive the drug.
Dr Julie Jonsson, a senior research officer in the Department, discovered the drug, Captopril, had an impact on the development of blood vessels during her PhD research at the University.
'While Captopril on young rats results in restricted and fragile blood vessels, the vascular effects of Captopril on adult rats are less pronounced,' Mrs Hii said.
'This suggests that Captopril may influence angiogenesis without conspicuous effects on established blood vessels.'
Mrs Hii's research was made possible through the generosity of graduate and Brisbane urologist Dr Les Thompson, of the Wesley Medical Centre.
Dr Thompson donated $75,000 to the University's Annual Appeal over the last three years to fund the scholarship within the University's Surgery Department.
The research has built on renal cell carcinoma research already carried out by Drs Nicol and Gotley.
For more information, contact Mrs Hii (telephone 07 3240 7146).
