Pancreatic cancer associated with obesity and diabetes: an alternative approach for its targeting

被引:82
作者
Pothuraju, Ramesh [1 ]
Rachagani, Satyanarayana [1 ]
Junker, Wade M. [1 ,2 ]
Chaudhary, Sanjib [1 ]
Saraswathi, Viswanathan [3 ]
Kaur, Sukhwinder [1 ]
Batra, Surinder K. [1 ,4 ,5 ]
机构
[1] Univ Nebraska Med Ctr, Dept Biochem & Mol Biol, Omaha, NE 68198 USA
[2] Univ Nebraska Med Ctr, Sanguine Diagnost & Therapeut, Omaha, NE USA
[3] Univ Nebraska Med Ctr, Dept Cellular & Integrat Physiol, Omaha, NE USA
[4] Univ Nebraska Med Ctr, Fred & Pamela Buffet Canc Ctr, Omaha, NE 68198 USA
[5] Univ Nebraska Med Ctr, Eppley Inst Res Canc & Allied Dis, Omaha, NE USA
关键词
Pancreatic cancer; Obesity; Insulin resistance; Diabetes; Adiponectin; Leptin; Gut microbiota; Inflammation; HEPATOCYTE GROWTH-FACTOR; MONOCYTE DIFFERENTIATION ANTIGEN; NECROSIS-FACTOR-ALPHA; INSULIN-RESISTANCE; HIGH-FAT; GENE-EXPRESSION; INTRAEPITHELIAL NEOPLASIA; THERAPEUTIC IMPLICATIONS; DUCTAL ADENOCARCINOMA; MOLECULAR BIOMARKERS;
D O I
10.1186/s13046-018-0963-4
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
BackgroundPancreatic cancer (PC) is among foremost causes of cancer related deaths worldwide due to generic symptoms, lack of effective screening strategies and resistance to chemo- and radiotherapies. The risk factors associated with PC include several metabolic disorders such as obesity, insulin resistance and type 2 diabetesmellitus (T2DM). Studies have shown that obesity and T2DM are associated with PC pathogenesis; however, their role in PC initiation and development remains obscure.Main bodySeveral biochemical and physiological factors associated with obesity and/or T2DM including adipokines, inflammatory mediators, and altered microbiome are involved in PC progression and metastasis albeit by different molecular mechanisms. Deep understanding of these factors and causal relationship between factors and altered signaling pathways will facilitate deconvolution of disease complexity as well as lead to development of novel therapies. In the present review, we focuses on the interplay between adipocytokines, gut microbiota, adrenomedullin, hyaluronan, vanin and matrix metalloproteinase affected by metabolic alteration and pancreatic tumor progression.ConclusionsMetabolic diseases, such as obesity and T2DM, contribute PC development through altered metabolic pathways. Delineating key players in oncogenic development in pancreas due to metabolic disorder could be a beneficial strategy to combat cancers associated with metabolic diseases in particular, PC.
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页数:15
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