News release

From: Garvan Institute of Medical Research

A metabolism switch that could help stop the spread of pancreatic cancer

Scientists identify a molecule that fuels pancreatic cancer spread to the liver, opening new avenues for treatment.

Researchers at the Garvan Institute of Medical Research have uncovered how pancreatic cancer hijacks a crucial metabolism ‘switch’ to help it spread, revealing a potential new treatment strategy for this highly aggressive disease.

The study, published in Science Advances, identifies the molecule Neuropeptide Y (NPY) as a key driver of pancreatic cancer metastasis – the process by which cancer spreads to other organs.

“NPY is a signalling molecule best known for its role in regulating metabolism, appetite and satiety. We found NPY to be significantly higher in pancreatic cancer cells compared to normal tissue,” says Dr David Herrmann, senior author of the study and Group Leader at Garvan.

“By blocking NPY’s function in mouse models, we found we could substantially reduce the spread of pancreatic cancer to the liver, the most common site of metastasis in patients. These preliminary findings reveal this molecule as a promising target to investigate further for pancreatic cancer.”

Slowing pancreatic cancer

Pancreatic cancer is one of the deadliest forms of cancer, with an average five-year survival rate of just 13%. More than 80% of patients are diagnosed at an advanced stage when surgery is no longer an option. With metastasis a major factor in the lethality of the disease, developing treatments that can prevent cancer from spreading is critically important.

“Our research shows that pancreatic cancer hijacks a molecule known for regulating physiological processes, such as food intake and energy balance, and uses it to promote its own spread,” says first author Dr Cecilia Chambers, who completed the study as a PhD researcher at Garvan. “By blocking this molecule, we could slow down pancreatic cancer cell movement and metastatic outgrowth in the liver thereby limiting the spread of the cancer.”

The study is the first time the role of NPY has been investigated in pancreatic cancer metastasis, building on previous research that linked the molecule to cancer progression in breast, prostate and neuroblastoma cancers.

“Surprisingly, in addition to the anti-metastatic effect we observed, blocking NPY also helped reduce the loss of muscle and fat tissue mass – known as cachexia – that often accompanies cancer progression. This additional benefit to maintain muscle and fat tissue could be crucial for patients to tolerate chemotherapy and other treatments,” says Dr David Herrmann, senior author of the study and Group Leader at Garvan.

New avenues for personalised treatment

These findings could pave the way for more targeted treatments, explains Professor Paul Timpson, Head of the Invasion and Metastasis Lab at Garvan: “We found particularly high levels of NPY in highly aggressive and metastatic pancreatic cancers. This suggests that blocking NPY could be an effective personalised treatment for this subset of patients, as well as those who experience severe weight loss due to cancer.”

Following their promising findings, the researchers developed an antibody designed to neutralise NPY’s effect in cancer, which they are now testing in mouse models and in tissues donated by pancreatic cancer patients.

Moving discovery toward clinical trials

While the study provides preliminary evidence that inhibiting NPY may reduce cancer spread and reduce weight loss, the research team is now working to optimise how this strategy could be combined with existing treatments.

“One of our next steps is to refine how we use this approach in combination with chemotherapy,” says Dr Herrmann. “There’s growing evidence that timing is critical – thus determining whether NPY inhibition is most effective when introduced before or after chemotherapy is important. Understanding this will be key to translating our findings into clinical trials, and ultimately to improve the outcomes of this disease.”

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