Protein-mapping technology helps identify mutations in drug-resistant cells as award-winning cancer treatment research continues
The Childrens Cancer Institute Australia (CCIA) is leading the fight against drug-resistant cancer using advanced protein-mapping technology from GE Healthcare.
Two-dimensional gel technology called Dige (2D fluorescence difference gel electrophoresis), developed by GE Healthcare, is being used to study variations in the protein make-up of cancer cells that do not respond to chemotherapy treatment.
The technology forms part of ongoing CCIA research that has led to a breakthrough discovery of cell mutations that confer resistance to anti-cancer drugs.
Originally known as the Children's Leukaemia and Cancer Foundation, CCIA was founded in 1976 by a dedicated group of parents and doctors of children with cancer.
At the time there was no other organisation in Australia carrying out research into childhood cancer, and today CCIA remains the only independent research institute in the country devoted to researching the causes, prevention and cure of childhood cancer.
CCIA group leader Maria Kavallaris said her research is currently focused on drug resistance in acute lymphoblastic leukaemia, the most common type of cancer in children up to 14 years of age.
Approximately 500 Australian children a year are diagnosed with cancer, with the overall the survival rate improving to about seven out of ten.
"Some cancer cells dont die when they're exposed to certain types of anti-cancer drugs; they may respond initially, but as treatment progresses a small number of cells can survive", said Kavallaris.
"In this way a patient may be doing well on the initial treatment, but when the cancer returns, the same drugs have no effect.
"It is this resistance to treatment that were studying in an effort to understand why it happens and find solutions to the problem".
Kavallaris said there is evidence that cancer cells can acquire resistance to certain drugs during treatment, and that some types of cancer cells are intrinsically resistant to those drugs.
"Before we can start looking for new therapies and treatments, we first need to understand the triggers for acquired and intrinsic resistance to existing treatments", she said.
"We do that by identifying the proteins and protein pathways involved in drug resistance.
"Since proteins confer function in a cell - and the majority of today's anti-cancer drugs target proteins - by studying the protein profiles of drug-resistant cells we can hopefully determine where resistance occurs, why it occurs, and how to overcome it.
"This is where GE Healthcare's Dige technology is so helpful, because it allows us to study variations in or mutations of drug-resistant cell proteins faster and more accurately than was ever possible before", she adds.
"Dige uses special dyes called CyDye to label proteins in sensitive and resistant cells, which are then separated, laser-scanned and analysed using DeCyder software from GE Healthcare to spot differences as small as 10% between protein samples.
"We can therefore quickly see which proteins have been lost, added or mutated in the resistant cells, and determine if and how they contribute to resistance".
According to Kavallaris, the difference between using Dige and older protein analysis techniques is literally months of time saved: "Because of gel-to-gel variations, we previously had to use three to five replicate gels of each protein sample to get anywhere near the statistical accuracy we needed.
"With Dige and CyDye we can use three protein samples per gel and get up to 95% statistical accuracy.
"We're confident in the data we're getting because we use other techniques to verify our Dige results".
Using different protein and gene analysis techniques, including Dige, CCIA researchers have identified a protein mutation in leukaemia cells that contributes to resistance against certain drugs, a discovery that was recently recognised at an international research meeting in Montreal, Canada.
CCIA postgraduate student Nicole Verrills, has further extended these initial studies using a clinically relevant model of acute lymphoblastic leukaemia, earning her a share of the Cass Foundation Best of the Best award at the 2004 Australian Health and Medical Research Congress in Sydney.
"Technology like Dige speeds up the process, improves accuracy, and delivers reproducible results that are helping us find answers to the many questions we still have about the treatments weve developed and continue to develop", Kavallaris said.
Peter Simpson, general manager Australasia, GE Healthcare biosciences, said the fight against cancer is not new, nor is it likely to end anytime soon, but with signs that survival rates have increased substantially in the past 30 to 40 years steady progress is being made.
"We are working closely with researchers, doctors, technicians and analysts from around the world in the hope that, through the ongoing development of our technology and advanced research techniques in the field, new and better ways can be found to combat the disease that affects so many Australian lives today".
