2025 New Treatment - Dr. Zaklina Kovacevic

Pancreatic cancer is one of the deadliest cancers, partly because it's often diagnosed too late and quickly becomes resistant to available treatments. A big reason for this resistance is the tumour microenvironment—a thick layer of non-cancerous cells and proteins that surrounds the tumour and protects it from attack.

Among the most important players in this environment are fibroblasts—normal support cells found in connective tissue. In pancreatic cancer, these fibroblasts get hijacked by cancer cells and transform into a harmful version called cancer-associated fibroblasts (CAFs). These CAFs multiply rapidly and build a dense web of protein that acts like a shield, keeping out immune cells that could otherwise attack the cancer.

Even when immune cells do manage to enter the tumour, they are quickly switched off by chemicals released by both the cancer cells and the CAFs. On top of that, CAFs help cancer cells resist chemotherapy by releasing nutrients and growth signals that protect them.

Although CAFs are now recognised as a major reason why pancreatic cancer is so hard to treat, there are still no therapies that successfully target them. In fact, previous attempts to remove CAFs completely have actually made things worse and failed in clinical trials. Since then, scientists have discovered that not all CAFs are bad—some can actually help the immune system fight cancer.

This means that the real breakthrough will come not from eliminating all CAFs, but from selectively removing the harmful ones while keeping the helpful ones.

Our research has identified key metabolic differences between these two types of CAFs. We’ve found that it's possible to target the harmful CAFs using drugs that are already available and known to interfere with cell metabolism. This opens the door to a new treatment strategy that combines these metabolic-targeting drugs with standard chemotherapy and new targeted treatments—making therapy more effective by weakening the tumour’s defences. We already have promising results showing that this combination approach can significantly slow down tumour growth—much more effectively than any single treatment on its own. Even more excitingly, this strategy deactivates the harmful CAFs while preserving the helpful ones.

In this project, we will investigate the potential of this treatment using advanced models that closely mimic how human pancreatic tumours behave. These include lab-grown mini-tumours and patient-derived tumoroids—tiny, 3D versions of real tumours that maintain all the key cell types found in actual pancreatic cancer.

Once we identify the most effective treatment combinations, we’ll test them in established mouse models of pancreatic cancer to evaluate how well they work and how safe they are. This will generate the essential data needed to move this promising new treatment strategy toward clinical trials and real-world use.