Researchers publish ‘playbook’ for understanding pancreatic cancer, one of the deadliest cancers

Posted on: 30 April 2026

Pancreatic cancer has the worst survival rate of any major cancer, with just 13% of patients alive five years after diagnosis. Late detection, aggressive tumour biology, limited treatment options and less research funding, has meant progress has been frustratingly slow.

Now, scientists at the Trinity St James’s Cancer Institute (TSJCI), the first comprehensive cancer centre in Ireland, have taken a different approach: instead of focusing on a single biological pathway or target, they have assembled a comprehensive “playbook” of the disease, showing how multiple biological systems interact to drive its growth. Published in the prestigious journal Cancer Letters, the comprehensive review applies the most up-to-date “Hallmarks of Cancer” framework - a globally recognised generic model describing the essential traits of cancer, first developed in 2000 by Douglas Hanahan and Robert Weinberg - to pancreatic cancer in unprecedented detail.

Rather than treating pancreatic cancer as a single problem, the paper describes how it is driven by a complex network of factors, including: genetic mutations, the tumour microenvironment, immune system evasion, metabolic changes, tumour-nerve interactions, and even the microbiome.

By integrating the findings from hundreds of studies across these multiple areas, the review highlights how these processes work together, not in isolation, to make pancreatic cancer so difficult to treat.

Lead author Dr Laura Kane, Research Ireland Postdoctoral Research Fellow, said:

“Pancreatic cancer is not driven by one pathway, it’s a highly coordinated system. What we’ve done is bring all of that complexity together into a single, usable framework. By showing how these different mechanisms connect, we can start to see where the real vulnerabilities of the disease may lie.”

Crucially, the study moves beyond simply summarising existing research. It identifies where scientific understanding is strongest, where gaps remain, and where future efforts should be focused.

One of the key messages is that single-drug approaches are unlikely to succeed. Instead, the authors argue that progress will depend on smarter, combination-based treatments that target multiple hallmarks of the disease at once. This shift in thinking could have important implications for how clinical trials are designed and how new therapies are developed.

Senior author Professor Stephen Maher, Professor in Translational Oncology, added:

“Despite decades of research, outcomes for pancreatic cancer patients have improved only marginally. This paper helps explain why. It also provides a roadmap for designing the next generation of treatments, ones that reflect the true complexity of the disease.”

The review is particularly relevant for clinicians and researchers, but also offers important insights for patients and families by explaining why pancreatic cancer has proven so resistant to treatment, and where new hope may emerge.

Looking ahead, the team emphasises the need for: biomarker-led clinical trials, better laboratory models that reflect real tumour complexity, and more integrated approaches to targeting the disease.

By bringing together the latest advances across multiple fields, this work provides one of the most comprehensive overviews of pancreatic cancer to date, and a clearer path toward more effective treatments.

READ: The full paper: The Hallmarks of Pancreatic Cancer can be viewed at the following link here:https://doi.org/10.1016/j.canlet.2026.218437

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