2025 New Treatment Accelerator - Prof Marina Pajic

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest forms of cancer and  is very difficult to treat. One reason for this is that PDAC is very different from person to  person. Personalised medicine, which is tailoring treatment to the specific molecular features of a patient’s cancer, is a promising strategy for targeting these differences in  PDAC. 

New research has improved our understanding of pancreatic cancer and why it's so  resistant to treatment. Pancreatic tumours are surrounded by tough scar-like tissue that  blocks drugs from getting into the tumour and sends signals to cancer cells stimulating  their ability to grow and spread. This tough scar tissue is made up of proteins and cells  that are corrupted by cancer cells which act as a protective barrier against therapies. 

A group of proteins called integrins help cells stick to their surrounding tissues and  communicate, helping to maintain normal cell behaviour including growth and  movement. Normal integrin function is often disrupted in cancers, resulting in tumour growth, invasion and spread, altering the surrounding environment contributing to the scar tissue. Because of this, integrins have become a highly attractive target for new  cancer treatments. 

Our research has shown that targeting certain integrins can weaken the tumour’s protective barrier and make treatments like chemotherapy and immunotherapy work  better. Collaborating with Pliant Therapeutics, we’re testing new small molecule  inhibitors that block specific integrin proteins (αVβ8 and αVβ1), which are known to  promote pancreatic cancer progression. These new therapies are already showing  promising results in our hands when combined with standard of care cancer  treatments, such as chemotherapy. In this project, we plan to dive deeper by studying  individual cancer cells to understand exactly how these new treatments work and to  find markers (called biomarkers) that can tell us which patients are most likely to  benefit. We’ll use advanced tools to study DNA and proteins to see how cancer  responds to treatment at the single-cell level. 

By combining our earlier findings with our experience in developing targeted therapies,  we aim to: 

1. Find reliable indicators that predict which patients will respond well to  treatment. 

2. Better understand how integrin-targeted therapies work at a molecular level. 

3. Explore how these therapies change both the cancer cells and the surrounding  tumour environment. 

Ultimately, this research could lead to targeted, more personalised treatment options  for pancreatic cancer patients - and potentially reduce the number of lives lost to this  aggressive disease. 

This grant was made possible by Woolworths' Woolies Wheels and Walks in partnership with Tour de Cure.