PMID- 30567565 OWN - NLM STAT- MEDLINE DCOM- 20190212 LR - 20220330 IS - 1756-9966 (Electronic) IS - 0392-9078 (Print) IS - 0392-9078 (Linking) VI - 37 IP - 1 DP - 2018 Dec 19 TI - Pancreatic cancer associated with obesity and diabetes: an alternative approach for its targeting. PG - 319 LID - 10.1186/s13046-018-0963-4 [doi] LID - 319 AB - BACKGROUND: Pancreatic 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 diabetes mellitus (T2DM). Studies have shown that obesity and T2DM are associated with PC pathogenesis; however, their role in PC initiation and development remains obscure. MAIN BODY: Several 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. CONCLUSIONS: Metabolic 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. FAU - Pothuraju, Ramesh AU - Pothuraju R AD - Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA. FAU - Rachagani, Satyanarayana AU - Rachagani S AD - Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA. FAU - Junker, Wade M AU - Junker WM AD - Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA. AD - Sanguine Diagnostics and Therapeutics, University of Nebraska Medical Center, Omaha, NE, USA. FAU - Chaudhary, Sanjib AU - Chaudhary S AD - Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA. FAU - Saraswathi, Viswanathan AU - Saraswathi V AD - Department of Cellular & Integrative Physiology, University of Nebraska Medical Center, Omaha, NE, USA. FAU - Kaur, Sukhwinder AU - Kaur S AD - Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA. FAU - Batra, Surinder K AU - Batra SK AD - Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA. sbatra@unmc.edu. AD - Fred & Pamela Buffet Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA. sbatra@unmc.edu. AD - Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, USA. sbatra@unmc.edu. LA - eng GR - R01 CA206444/CA/NCI NIH HHS/United States GR - RO1 CA210637, RO1CA206444, and RO1 CA183459, UO1 CA200466, P50 CA127297 and PO1 CA217798/National Institutes of Health/ GR - U01 CA200466/CA/NCI NIH HHS/United States GR - P50 CA127297/CA/NCI NIH HHS/United States GR - R01 CA183459/CA/NCI NIH HHS/United States GR - R01 CA210637/CA/NCI NIH HHS/United States GR - P01 CA217798/CA/NCI NIH HHS/United States PT - Journal Article PT - Review DEP - 20181219 PL - England TA - J Exp Clin Cancer Res JT - Journal of experimental & clinical cancer research : CR JID - 8308647 SB - IM MH - Animals MH - Diabetes Mellitus, Type 2/*complications/pathology MH - Humans MH - Obesity/*complications/pathology MH - Pancreatic Neoplasms/*etiology/pathology MH - Risk Factors PMC - PMC6299603 OTO - NOTNLM OT - Adiponectin OT - Diabetes OT - Gut microbiota OT - Inflammation OT - Insulin resistance OT - Leptin OT - Obesity OT - Pancreatic cancer COIS- ETHICS APPROVAL AND CONSENT TO PARTICIPATE: Not applicable CONSENT FOR PUBLICATION: All authors read and approved the final manuscript. COMPETING INTERESTS: SKB is one of the co-founders of Sanguine Diagnostics and Therapeutics, Inc. WMJ is Chief Scientific Officer of Sanguine Diagnostics and Therapeutics, Inc. Other authors declare no competing interests. PUBLISHER'S NOTE: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. EDAT- 2018/12/21 06:00 MHDA- 2019/02/13 06:00 PMCR- 2018/12/19 CRDT- 2018/12/21 06:00 PHST- 2018/08/28 00:00 [received] PHST- 2018/11/14 00:00 [accepted] PHST- 2018/12/21 06:00 [entrez] PHST- 2018/12/21 06:00 [pubmed] PHST- 2019/02/13 06:00 [medline] PHST- 2018/12/19 00:00 [pmc-release] AID - 10.1186/s13046-018-0963-4 [pii] AID - 963 [pii] AID - 10.1186/s13046-018-0963-4 [doi] PST - epublish SO - J Exp Clin Cancer Res. 2018 Dec 19;37(1):319. doi: 10.1186/s13046-018-0963-4.