Both type 2 (T2DM) and type 1 (T1DM) diabetes mellitus confer an increased risk of pancreatic cancer in humans. The magnitude and temporal trajectory of the risk conferred by the two forms of diabetes are similar, suggesting a common mechanism. Carbonyl stress is a hallmark of hyperglycemia and dyslipidemia, which accompanies T2DM, prediabetes, and obesity. Accumulating evidence demonstrates that diabetes promotes pancreatic ductal adenocarcinoma (PDAC) in experimental models of T2DM, a finding recently confirmed in a T1DM model. The carbonyl stress markers advanced glycation end-products (AGEs), the levels of which are increased in diabetes, were shown to markedly accelerate tumor development in a mouse model of Kras-driven PDAC. Consistently, inhibition of AGE formation by trapping their carbonyl precursors (i.e., reactive carbonyl species, RCS) prevented the PDAC-promoting effect of diabetes. Considering the growing attention on carbonyl stress in the onset and progression of several cancers, including breast, lung and colorectal cancer, this review discusses the mechanisms by which glucose and lipid imbalances induce a status of carbonyl stress, the oncogenic pathways activated by AGEs and their precursors RCS, and the potential use of carbonyl-scavenging agents and AGE inhibitors in PDAC prevention and treatment, particularly in high-risk diabetic individuals.

Diabetes and pancreatic cancer-a dangerous liaison relying on carbonyl stress / Menini, S.; Iacobini, C.; Vitale, M.; Pesce, C.; Pugliese, G.. - In: CANCERS. - ISSN 2072-6694. - 13:2(2021), pp. 1-26. [10.3390/cancers13020313]

Diabetes and pancreatic cancer-a dangerous liaison relying on carbonyl stress

Menini S.
Co-primo
Writing – Original Draft Preparation
;
Iacobini C.
Co-primo
Writing – Review & Editing
;
Vitale M.;Pugliese G.
Ultimo
2021

Abstract

Both type 2 (T2DM) and type 1 (T1DM) diabetes mellitus confer an increased risk of pancreatic cancer in humans. The magnitude and temporal trajectory of the risk conferred by the two forms of diabetes are similar, suggesting a common mechanism. Carbonyl stress is a hallmark of hyperglycemia and dyslipidemia, which accompanies T2DM, prediabetes, and obesity. Accumulating evidence demonstrates that diabetes promotes pancreatic ductal adenocarcinoma (PDAC) in experimental models of T2DM, a finding recently confirmed in a T1DM model. The carbonyl stress markers advanced glycation end-products (AGEs), the levels of which are increased in diabetes, were shown to markedly accelerate tumor development in a mouse model of Kras-driven PDAC. Consistently, inhibition of AGE formation by trapping their carbonyl precursors (i.e., reactive carbonyl species, RCS) prevented the PDAC-promoting effect of diabetes. Considering the growing attention on carbonyl stress in the onset and progression of several cancers, including breast, lung and colorectal cancer, this review discusses the mechanisms by which glucose and lipid imbalances induce a status of carbonyl stress, the oncogenic pathways activated by AGEs and their precursors RCS, and the potential use of carbonyl-scavenging agents and AGE inhibitors in PDAC prevention and treatment, particularly in high-risk diabetic individuals.
2021
carnosine derivatives; epithelial growth factor receptor; hyperglycemia; methylglyoxal; obesity; pancreatic ductal adenocarcinoma; reactive carbonyl species; receptor for advanced glycation end-products; yes-associated protein
01 Pubblicazione su rivista::01g Articolo di rassegna (Review)
Diabetes and pancreatic cancer-a dangerous liaison relying on carbonyl stress / Menini, S.; Iacobini, C.; Vitale, M.; Pesce, C.; Pugliese, G.. - In: CANCERS. - ISSN 2072-6694. - 13:2(2021), pp. 1-26. [10.3390/cancers13020313]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1486095
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