Obesity associated pancreatic ductal adenocarcinoma: Therapeutic challenges

Obesity is a prominent health issue worldwide and directly impacts pancreatic health, with obese individuals exhibiting a significant risk for increasing pancreatic ductal adenocarcinoma (PDAC). Several factors potentially explain the increased risk for the development of PDAC, including obesity-ind...

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Bibliographic Details
Published in:Seminars in cancer biology 2023-12, Vol.97, p.12-20
Main Authors: Srilatha, Mundla, Malla, Ramarao, Adem, Megha Priya, Foote, Jeremy B, Nagaraju, Ganji Purnachandra
Format: Article
Language:English
Subjects:
Carcinogenesis
Carcinoma, Pancreatic Ductal - complications
Carcinoma, Pancreatic Ductal - therapy
Humans
Inflammation - complications
Obesity - complications
Obesity - metabolism
Pancreatic Neoplasms - drug therapy
Pancreatic Neoplasms - therapy
Tumor Microenvironment
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Summary:Obesity is a prominent health issue worldwide and directly impacts pancreatic health, with obese individuals exhibiting a significant risk for increasing pancreatic ductal adenocarcinoma (PDAC). Several factors potentially explain the increased risk for the development of PDAC, including obesity-induced chronic inflammation within and outside of the pancreas, development of insulin resistance and metabolic dysfunction, promotion of immune suppression within the pancreas during inflammation, pre- and malignant stages, variations in hormones levels (adiponectin, ghrelin, and leptin) produced from the adipose tissue, and acquisition of somatic mutations in tumor once- and suppressor proteins critical for pancreatic tumorigenesis. In this manuscript, we will explore the broad impact of these obesity-induced risk factors on the development and progression of PDAC, focusing on changes within the tumor microenvironment (TME) as they pertain to prevention, current therapeutic strategies, and future directions for targeting obesity management as they relate to the prevention of pancreatic tumorigenesis.
ISSN:1044-579X
1096-3650
DOI:10.1016/j.semcancer.2023.11.002