Cancer researchers spend their days working tirelessly crunching data, peering through microscopes, and examining findings in hope they discover a breakthrough that will help them get a step closer to finding a cure.
The team over at the Garvan Institute of Medical Research have been doing just that to fight pancreatic cancer.
Dr Paul Timpson, Head of Garvan’s Invasion and Metastasis Laboratory and who co-led the study with Dr Marina Pajic, said the study looked into attacking the “Achilles heel” of pancreatic cancer using Fasudil, a drug that targets a protein called ROCK and is currently used in Japan to treat stroke patients, over a short three-day period. Initial tests carried out on mice and patient samples from the Australian Pancreatic Cancer Genome Initiative showed survival rates doubled and the spread of cancer to other tissues was impaired. The findings have been published in Science Translational Medicine. According to Dr Timpson, pancreatic tumours are surrounded by a dense stiff tissue made of cells and blood vessels known as stroma in which it “nests” in and encourages the survival and progression of the tumour. The stroma also acts like a protective shield against chemotherapy.
However, the team discovered that by using Fasudil to attack the stroma first rather than the tumour – which previous studies have done – it softens the hold of the stroma making the become more susceptible when the cancer is then treated with standard-of-care chemotherapy.
“There has been a heated and longstanding controversy in cancer research about whether targeting the stroma can making pancreatic tumours more susceptible to therapy,” he said.
“I think we have resolved the debate. We’ve been able to show for the first time that it’s crucial to treat the stroma first and the tumour second, and to fine-tune the treatment timing to maximise outcome, wtumour hile minimising side effects.”
Dr Timpson attributed the success of the study to the team’s ability to carry out intravital microscopy techniques using “one of the most technical microscopes”, giving the team the chance to examine pancreatic cancer in real-time, and how the tumour and the stroma was reacting to Fasudil.
However, Timpson added while it’s a significant step forward, it’s only the start of a long journey. The team plans to work closely to translate these findings into early-stage clinical study to examine the safety of this approach through a two-prong approach: The first is to repurpose Fausdil from cardiovascular to pancreatic cancer use by performing phase I safety checks for its application with subsequent chemotherapy; and the second is to collaborate with other large scale pharmaceutical companies who have their own new age ROCK inhibitors that are currently in phase I testing for other disease setting.
Nevertheless, the finding gives renewed hope to fight pancreatic cancer, dubbed the “silent killer.” The current five-year survival rate of pancreatic cancer is 7% – a result that has not improved for 40 years.
“It was previously one treatment for all. This is why personalised treatment is the future; treat the patients you can because it means they will survive, but don’t give it to people where you know it won’t work,” Dr Timpson said.
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