Abstract
Pancreatic ductal adenocarcinoma (PDAC) is the most common form of pancreatic cancer and carries a dismal prognosis. Resectable patients are treated predominantly with surgery while borderline resectable patients may receive neoadjuvant treatment (NAT) to downstage their disease prior to possible resection. PDAC tissue is stiffer than healthy pancreas, and tissue stiffness is associated with cancer progression. Another feature of PDAC is increased tissue heterogeneity. We postulate that tumour stiffness and heterogeneity may be used alongside currently employed diagnostics to better predict prognosis and response to treatment. In this review we summarise the biomechanical changes observed in PDAC, explore the factors behind these changes and describe the clinical consequences. We identify methods available for assessing PDAC biomechanics ex vivo and in vivo, outlining the relative merits of each. Finally, we discuss the potential use of radiological imaging for prognostic use.
Highlights
Pancreatic cancer is the fourth leading cause of cancer related mortality in the US and Europe [1,2], and is projected to become the second leading cause by 2030 [3]
The elaboration of an extensive extracellular matrix (ECM) is the key driver of increased stiffness in Pancreatic ductal adenocarcinoma (PDAC)
Recent proteomic analysis of stromal composition reveals that while both cancer cells and cancer associated fibroblast (CAF) contribute to stromal matrix elaboration, tumour cell derived proteins were correlated with poor patient survival and metastasis [64,65]
Summary
Pancreatic cancer is the fourth leading cause of cancer related mortality in the US and Europe [1,2], and is projected to become the second leading cause by 2030 [3]. It exhibits a remarkable resistance to conventional treatment options including chemotherapy, radiotherapy, and immunotherapy [8,9]. This leaves surgery as the only potentially curative option, and for the 10–20% of patients who undergo surgical resection, the five-year survival rate is 15–25% [10]. Tumour changes from healthy pancreas to pancreatic ductal adeFigure 1. Schematicillustration illustrationofof tumour changes from healthy pancreas to pancreatic ductal nocarcinoma (PDAC). Bottom: Schematic representation of cell–cell and cell–extracellular matrix and resected PDAC tissue. Bottom: Schematic representation of cell–cell and cell–extracellular matrix (ECM) interactions interactions in in healthy healthy pancreas pancreas and and PDAC.
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