Poster Presentation 37th Lorne Cancer Conference 2025

Expression and localisation of cell death regulators in pancreatic adenocarcinoma (#228)

Trinity Peachey 1 , Ka Yee Fung 1 , Peter Gibbs 1 2 , Hue Mai La 3 , Paul Nguyen 3 , Jacek Marzec 3 , Sehrish Kanwal 3 , Belinda Lee 1 , Sean Grimmond 3 , Tracy Putoczki 1 2 4
  1. WEHI, Melbourne, VIC, Australia
  2. Department of Medical Biology, University of Melbourne, Melbourne, VIC, Australia
  3. Centre for Cancer Research, University of Melbourne, Melbourne, VIC, Australia
  4. Department of Surgery, University of Melbourne, Melbourne, VIC, Australia

Pancreatic Adenocarcinoma (PAAD) is the 12th most commonly diagnosed cancer, and yet is the 6th leading cause of cancer-associated mortality worldwide, with a 5-year relative survival rate of below 13% in Australia (1,2). While other cancers (e.g. lung, prostate, breast) have experienced declining mortality rates, PAAD is predicted to become the second leading cause of cancer-associated mortality within the next ten years (1,2). This disease has a distinct lack of effective treatment options, necessitating novel therapeutic targets and strategies.

One hallmark of cancer is its evasion of cell death, with PAAD being particularly resistant to programmed cell death (3). Upregulated expression of anti-apoptotic proteins has been found in various cancers and has been shown to contribute to chemo-resistance (4). However, a thorough characterisation of the components of the intrinsic and extrinsic cell death pathways, and their role in PAAD has yet to be fully elucidated.

We utilised tissue samples from PAAD patients enrolled in the PURPLE Pancreatic Cancer Translational Registry and explored single nuclear (sn)RNA sequencing data to examine expression of components of the intrinsic and extrinsic cell death pathways. In parallel, we employed immunohistochemistry (IHC) to investigate the spatial localisation of these components within the tumour microenvironment. Prognostic association was determined by extracting the patient’s clinical history from our unique PURPLE translational registry. Our results demonstrated cell specific expression of cell death components within the PAAD microenvironment.  These studies will provide an opportunity to stratify patients based on integrated genomic and histopathological subtypes and to investigate the therapeutic potential of targeting cell death regulators in PAAD.

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