Making pancreatic cancer more receptive to treatment

Background

Each year, about 3,600 Australians are diagnosed with pancreatic cancer. This aggressive disease is often discovered quite late, but even in its early stages it can quickly spread through the body. Pancreatic cancer is known to be particularly resistant to chemotherapy, because the tumours are usually enveloped in extensive scar tissue which creates a physical barrier between the medication and the targeted tumour cells. The tumour recruits healthy cells surrounding the pancreas to create this scar tissue, helping the cancer to spread.

For the past 30 years there has been little improvement in the survival rates of pancreatic cancer, so there is an urgent need for new treatments that can effectively target the disease.

The research

Pancreatic cancer spreads with the help of scar tissue produced by a special type of healthy cell surrounding the tumour. Associate Professor Phillips and her team have discovered that these ‘helper’ cells, called pancreatic stellate cells, carry two specific proteins which could provide a key to stopping the spread of scar tissue.

Their results suggest that when the two proteins are inhibited, the pancreatic stellate cells slow down in growth and in scar tissue production. As there are no specific drugs known to inhibit these proteins, Associate Professor Phillips set out to develop a gene-based therapy.

The team has developed a nanomedicine-gene therapy (tiny drug delivery vehicles) to silence two target genes in pancreatic ‘helper’ cells. In pre-clinical testing, this cutting-edge gene therapy effectively reduced the production of scar tissue around pancreatic tumours. Most excitingly, the team found when they combined their gene-therapy with a chemotherapy drug commonly used to treat pancreatic cancer they could almost completely block the spread of pancreatic cancer to other parts of the body.

During this study, the team also observed that when their gene targets are upregulated (exhibiting increased production) survival outcomes were poorer, suggesting the genes could be an effective biomarker for patient outcomes.