2025 Early Detection Grant - Dr. Michaela Kindlova

Pancreatic cancer (PC), or its most common type, pancreatic ductal adenocarcinoma  (PDAC), has extremely low survival, in part due to the great difficulty health  professionals face in identifying the disease at an early stage. Our study aims to  improve early detection of PDAC by studying the features of abnormally growing cells  within pancreatic lesions. Our current understanding tends to attribute PDAC to  changes in our DNA sequence which impacts how the cells behave and divide.  However, there is a growing body of evidence showing that other factors might play a  role. Under certain circumstances, the functionality of our cells can be manipulated by  the addition of small chemical molecules onto the side of our DNA chains, without  changing DNA sequence itself. One of the most important type of these modifications is  called DNA methylation. Improper methylation can change how our cells function, and  it has been implicated in cancer development. We aim to answer two questions about  methylation in pancreatic cancer. Firstly, can methylation changes in pancreatic tissue  detect early cancer development? Secondly, can turning methylation “on or off” in  pancreatic cancer cells intervene in this process and what role does communication  with pancreatic stellate cells (PSCs) play? 

Through our collaboration with clinicians from the Princess Alexandra hospital (PAH)  and Royal Brisbane Women’s Hospital (RBWH) we have access to the pancreatic  tissues originating from two groups of patients at the highest risk of developing PDAC: 1.  those with pancreatic lesions containing abnormally growing cells, and 2. people with a  significant family history of PDAC. We will apply a new and innovative type of  sequencing technology to these samples that will allow us to detect differences in  methylation between the healthy tissues and the tissues with abnormal growth. Given  these differences, we aim to establish a protocol that enables us to turn on or off the methylation at these specific DNA locations, thereby correcting their faulty methylation  and restoring normal cellular function. Also, we will study the contribution of the PSCs,  the cells that closely interact with cancer cells and complicate the treatment by  creating an unapproachable layer around pancreatic tumour. 

Using cutting-edge sequencing technology will open the door to fully exploring the  connection between cancer and methylation changes. We believe that through this  research we can better understand PDAC and how methylation of our DNA impacts  cancer initiation and growth. Importantly, methylation is a reliable marker detectable in  a patient’s blood - we hope that in the future, our results will lay the foundation for using  methylation status as a biomarker of early cancer development leading to better  survival rates for PDAC patients.