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A drug that is already used to treat strokes can significantly prolong the survival of mice with pancreatic cancer.
Pancreatic cancer has the worst survival rate of any major cancer. The standard chemotherapy combination of gemcitabine and nab-paclitaxel (Abraxane) only keeps patients alive for an average of nine months. Treatment is difficult because pancreatic tumours are protected by an armour of connective tissue, blood vessels and immune cells, known collectively as the stroma.
Now, a team led by Paul Timpson and Marina Pajic at the Garvan Institute of Medical Research in Sydney, Australia, has shown that the stroke drug fasudil can weaken this stroma, making it easier for chemotherapy drugs to enter the tumour.
In mice with pancreatic cancer, three days of fasudil treatment prior to standard chemotherapy increased survival time by 47 per cent. If this benefit translated to humans, it would increase average survival from 9 to 13 months. “It doesn’t sound like much, but because the baseline success for pancreatic cancer treatments is so low, any improvement is fantastic,” says Timpson.
Using a type of microscopy that images live tumours, the team found that fasudil worked in two ways. As well as weakening the tumour, which makes it less able to grow and spread to other parts of the body, the drug made blood vessels become more leaky, enabling more chemotherapy drugs to spill into the tumour.
“The Achilles heel of pancreatic cancer cells is their need for the surrounding tissue to structure them and help them to grow and move,” says Timpson. “Attacking the stroma makes them disoriented.”
Large-scale studies have confirmed the safety of fasudil, which inhibits a type of protein called ROCK that stiffens blood vessels. In this way, the drug keeps blood vessels open in the brains of people who have had a stroke. Fasudil was approved in Japan in 1995, and is no longer covered by a patent, meaning it is cheap – although it is only currently used clinically in Asia.
That might change if fasudil finds a role in cancer treatment, says Pajic. The team is now looking at trialling the drug in combination with chemotherapy in people with pancreatic cancer, she says.
Ruth Ganss at the Harry Perkins Institute of Medical Research in Perth, Australia, says the finding that fasudil can remodel tumour stroma is remarkable. “Pancreatic cancers are stiff and known to contain lots of matrix,” she says. “This shows impressively that ROCK inhibition has very specific stromal effects and overall benefits.”
The same approach may be useful for boosting the effects of chemotherapy in other types of solid tumour with high levels of stroma, Ganss says.