Defining Parallels between the Salivary Glands and Pancreas to Better Understand Pancreatic Carcinogenesis: A Comparative Review

Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumor with a dismal prognosis, largely due to its late presentation. PDAC was ranked fourth in terms of tumor-related mortality in the Western world in 2015. This is at least in part due to its rapid spread in the asymptomatic phase of the disease. Methods for early detection, the development of reliable screening tools, and the identification of sensitive and specific biomarkers have remained essential research priorities to improve early patient management and outcomes. The pancreas and salivary glands share histological and functional similarities, and the salivary glands have demonstrated a role in oral and systemic health. This review focuses on the similarities and differences between the pancreas and salivary glands and how these can inform our understanding of PDAC genesis and early diagnosis. In particular, chemical exposure, which alters salivary gland gene transcription and morphogenesis, may not only directly impact salivary gland regulation but alter pancreatic function via the systemic secretion of growth hormones. Diabetes and obesity are associated with an increased risk of pancreatic cancer, and a link between chemical exposure and the development of diabetes, obesity, and consequently PDAC genesis is proposed. Possible mechanisms include altering salivary or pancreatic morphology and organ function, disrupting endocrine signaling, or altering pro-inflammatory homeostasis. Finally, saliva contains putative specific biomarkers that show promise as non-invasive diagnostic tools for PDAC. Finally, this review highlights the important role of the salivary glands and environmental factors on pancreatic homeostatic mechanisms and normal regulation through salivary gland dysfunction.