A 3D illustration of the male pancreas.Pancreatic cancer, one of the most deadly forms of the disease, can be stopped in its tracks by targeting an ‘Achilles heel’ protein, say scientists.
Blocking the molecule, called Yes-associated protein (Yap), did not prevent the disease from first developing but halted its growth.
Researchers hope the experiments, conducted on laboratory cell lines and mice, will one day lead to an effective treatment.
“We believe this is the true Achilles heel of pancreatic cancer, because knocking out Yap crushes this really aggressive cancer,” said US study leader Chunling Yi, from Georgetown University Medical Centre. “This appears to be the critical switch that promotes cancer growth and progression.”
Pancreatic cancer is often diagnosed late and has one of the worst cancer survival records.
Each year around 8,773 people in the UK develop the disease, and almost the same number – 8,320 – die from it.
We believe this is the true Achilles heel of pancreatic cancer, because knocking out Yap crushes this really aggressive cancer
Fewer than four per cent of those diagnosed with pancreatic cancer are still alive five years later.
Yap is over-active in pancreatic cancer and a number of other cancers, including those affecting the lungs, liver and stomach.
The new study, reported in the journal Science Signalling, involved mice with pancreatic ductal adenocarcinoma (PDAC), which accounts for 95 per cent of human pancreatic cancers.
Like humans with the disease, the mice have mutations in two key genes, Kras and p53.
It has proved very difficult to develop drugs that target either of these gene defects. But Yi’s team discovered links between Yap and both Kras and p53.
Kras activates Yap, and Yap shuts down p53 – an oncogene that offers protection from cancer when it is not faulty.
“The Kras mutation uses Yap to make cancer cells grow, so shutting down Yap defuses the mutated gene’s activity,” said Yi.
“Kras and p53 are two of the most mutated genes in human cancers, so our hope is that a drug that inhibits Yap will work in pancreatic cancer patients – who have both mutations – and in other cancers with one or both mutations.”