REFERENCES
2. Sridharan V, Hernandez-Barco YG, Ting DTJAoPC. Landscape of circulating diagnostic biomarkers in pancreatic malignancies. Ann Pancreat Cancer 2020;3:2616-741.
4. Palmeri M, Di Franco G, Bianchini M, et al. Prognostic impact of conservative surgery for pancreatic IPMNs. Surg Oncol 2021;38:101582.
5. Müller PC, Frey MC, Ruzza CM, et al. Neoadjuvant chemotherapy in pancreatic cancer: an appraisal of the current high-level evidence. Pharmacology 2021;106:143-53.
6. Conroy T, Hammel P, Hebbar M, et al. Canadian Cancer Trials Group and the Unicancer-GI-PRODIGE Group. FOLFIRINOX or gemcitabine as adjuvant therapy for pancreatic cancer. N Engl J Med 2018;379:2395-406.
7. Mehta A, Hwang WL, Weekes C. The present and future of systemic and microenvironment-targeted therapy for pancreatic adenocarcinoma. Ann Pancreat Cancer 2020;3:3-3.
8. Yu S, Zhang C, Xie KP. Therapeutic resistance of pancreatic cancer: roadmap to its reversal. Biochim Biophys Acta Rev Cancer 2021;1875:188461.
9. Tuerhong A, Xu J, Shi S, et al. Overcoming chemoresistance by targeting reprogrammed metabolism: the Achilles’ heel of pancreatic ductal adenocarcinoma. Cell Mol Life Sci 2021;78:5505-26.
10. Randazzo O, Cascioferro SM, Pecoraro C, et al. SF3B1 modulators affect key genes in metastasis and drug influx: a new approach to fight pancreatic cancer chemoresistance. Cancer Drug Resist 2021;4:904-22.
11. Aughton K, Elander NO, Evans A, et al. hENT1 predicts benefit from gemcitabine in pancreatic cancer but only with low CDA mRNA. Cancers (Basel) 2021;13:5758.
12. Du J, Gu J, Li J. Mechanisms of drug resistance of pancreatic ductal adenocarcinoma at different levels. Biosci Rep 2020;40:BSR20200401.
13. Saiki Y, Hirota S, Horii A. Attempts to remodel the pathways of gemcitabine metabolism: recent approaches to overcoming tumours with acquired chemoresistance. Cancer Drug Resist 2020;3:819-31.
14. Yi-zheng X, Plunkett W. Modulation of deoxycytidylate deaminase in intact human leukemia cells. Biochemical Pharmacology 1992;44:1819-27.
15. Heinemann V, Xu YZ, Chubb S et al. Cellular elimination of 2',2'-difluorodeoxycytidine 5'-triphosphate: a mechanism of self-potentiation. Cancer Res 1992;52:533-9.
16. Serdjebi C, Seitz JF, Ciccolini J, et al. Rapid deaminator status is associated with poor clinical outcome in pancreatic cancer patients treated with a gemcitabine-based regimen. Pharmacogenomics 2013;14:1047-51.
17. Miller AL, Garcia PL, Gamblin TL, Vance RB, Yoon KJ. Development of gemcitabine-resistant patient-derived xenograft models of pancreatic ductal adenocarcinoma. Cancer Drug Resist 2020;3:572-85.
18. Weizman N, Krelin Y, Shabtay-Orbach A, et al. Macrophages mediate gemcitabine resistance of pancreatic adenocarcinoma by upregulating cytidine deaminase. Oncogene 2014;33:3812-9.
19. Xiao H, Zheng Y, Ma L, Tian L, Sun Q. Clinically-relevant ABC transporter for anti-cancer drug resistance. Front Pharmacol 2021;12:648407.
20. Gupta SK, Singh P, Ali V, Verma M. Role of membrane-embedded drug efflux ABC transporters in the cancer chemotherapy. Oncol Rev 2020;14:448.
21. Xu M, Li L, Liu Z, et al. ABCB2 (TAP1) as the downstream target of SHH signaling enhances pancreatic ductal adenocarcinoma drug resistance. Cancer Lett 2013;333:152-8.
22. Lu Y, Xu D, Peng J, et al. HNF1A inhibition induces the resistance of pancreatic cancer cells to gemcitabine by targeting ABCB1. EBioMedicine 2019;44:403-18.
23. Okada Y, Takahashi N, Takayama T, Goel A. LAMC2 promotes cancer progression and gemcitabine resistance through modulation of EMT and ATP-binding cassette transporters in pancreatic ductal adenocarcinoma. Carcinogenesis 2021;42:546-56.
24. Boyd LNC, Andini KD, Peters GJ, Kazemier G, Giovannetti E. Heterogeneity and plasticity of cancer-associated fibroblasts in the pancreatic tumor microenvironment. Semin Cancer Biol 2022;82:184-96.
25. Jiang B, Zhou L, Lu J, et al. Stroma-targeting therapy in pancreatic cancer: one coin with two sides? Front Oncol 2020;10:576399.
26. Li MJAoPC. Preface for focused issue: science on pancreatic cancer. Ann Pancreat Cancer 2020;3:1.
27. Ni Y, Zhou X, Yang J, et al. The role of tumor-stroma interactions in drug resistance within tumor microenvironment. Front Cell Dev Biol 2021;9:637675.
28. Comandatore A, Immordino B, Balsano R, et al. Potential role of exosomes in the chemoresistance to gemcitabine and nab-paclitaxel in pancreatic cancer. Diagnostics (Basel) 2022;12:286.
29. Grasso C, Jansen G, Giovannetti E. Drug resistance in pancreatic cancer: impact of altered energy metabolism. Crit Rev Oncol Hematol 2017;114:139-52.
30. Dai S, Peng Y, Zhu Y, et al. Glycolysis promotes the progression of pancreatic cancer and reduces cancer cell sensitivity to gemcitabine. Biomed Pharmacother 2020;121:109521.
31. Masoud R, Reyes-Castellanos G, Lac S, et al. Targeting mitochondrial complex I overcomes chemoresistance in high OXPHOS pancreatic cancer. Cell Rep Med 2020;1:100143.
32. Reyes-Castellanos G, Masoud R, Carrier A. Mitochondrial metabolism in PDAC: from better knowledge to new targeting strategies. Biomedicines 2020;8:270.
33. Khoramipour K, Chamari K, Hekmatikar AA, et al. Adiponectin: structure, physiological functions, role in diseases, and effects of nutrition. Nutrients 2021;13:1180.
34. Esmaili S, Hemmati M, Karamian M. Physiological role of adiponectin in different tissues: a review. Arch Physiol Biochem 2020;126:67-73.
35. Choi HM, Doss HM, Kim KS. Multifaceted physiological roles of adiponectin in inflammation and diseases. Int J Mol Sci 2020;21:1219.
36. Lee YH, Magkos F, Mantzoros CS, Kang ES. Effects of leptin and adiponectin on pancreatic β-cell function. Metabolism 2011;60:1664-72.
37. Tao C, Sifuentes A, Holland WL. Regulation of glucose and lipid homeostasis by adiponectin: effects on hepatocytes, pancreatic β cells and adipocytes. Best Pract Res Clin Endocrinol Metab 2014;28:43-58.
38. Winzell MS, Nogueiras R, Dieguez C, Ahrén B. Dual action of adiponectin on insulin secretion in insulin-resistant mice. Biochem Biophys Res Commun 2004;321:154-60.
39. Bakhti M, Lickert H. New insights into β-cell failure, regeneration and replacement. Nat Rev Endocrinol 2022;18:79-80.
40. Tudurí E, Marroquí L, Soriano S, et al. Inhibitory effects of leptin on pancreatic alpha-cell function. Diabetes 2009;58:1616-24.
41. Tudurí E, Denroche HC, Kara JA, Asadi A, Fox JK, Kieffer TJ. Partial ablation of leptin signaling in mouse pancreatic α-cells does not alter either glucose or lipid homeostasis. Am J Physiol Endocrinol Metab 2014;306:E748-55.
42. Elinson N, Amichay D, Birk RZ. Leptin directly regulates exocrine pancreas lipase and two related proteins in the rat. Br J Nutr 2006;96:691-6.
43. Jiang CY, Wang W. Resistin aggravates the expression of proinflammatory cytokines in cerulein-stimulated AR42J pancreatic acinar cells. Mol Med Rep 2017;15:502-6.
44. Ramkissoon R, Gardner TB. Pancreatic steatosis: an update. Curr Opin Gastroenterol 2019;35:440-7.
45. Panagopoulou P, Fotoulaki M, Manolitsas A, Pavlitou-Tsiontsi E, Tsitouridis I, Nousia-Arvanitakis S. Adiponectin and body composition in cystic fibrosis. J Cyst Fibros 2008;7:244-51.
46. Polito R, Nigro E, Elce A, et al. Adiponectin expression is modulated by long-term physical activity in adult patients affected by cystic fibrosis. Mediators Inflamm 2019;2019:2153934.
47. Liu XX, Liu KY, Li P, Han S, Peng XD, Shen L. Adiponectin is expressed in the pancreas of high-fat-diet-fed mice and protects pancreatic endothelial function during the development of type 2 diabetes. Diabetes Metab 2014;40:363-72.
48. Muratore M, Komai AM. Theoretical study of the adiponectin receptors: binding site characterization and molecular dynamics of possible ligands for drug design. SN Appl Sci 2020:2.
49. Roy B, Palaniyandi SS. Tissue-specific role and associated downstream signaling pathways of adiponectin. Cell Biosci 2021;11:77.
50. Rubina KA, Semina EV, Kalinina NI, Sysoeva VY, Balatskiy AV, Tkachuk VA. Revisiting the multiple roles of T-cadherin in health and disease. Eur J Cell Biol 2021;100:151183.
51. Jiang J, Fan Y, Zhang W, et al. Adiponectin suppresses human pancreatic cancer growth through attenuating the β-catenin signaling pathway. Int J Biol Sci 2019;15:253-64.
52. Kato M, Watabe K, Tsujii M, Funahashi T, Shimomura I, Takehara T. Adiponectin inhibits murine pancreatic cancer growth. Dig Dis Sci 2014;59:1192-6.
53. Huang B, Cheng X, Wang D, et al. Adiponectin promotes pancreatic cancer progression by inhibiting apoptosis via the activation of AMPK/Sirt1/PGC-1α signaling. Oncotarget 2014;5:4732-45.
54. Bao Y, Giovannucci EL, Kraft P, et al. A prospective study of plasma adiponectin and pancreatic cancer risk in five US cohorts. J Natl Cancer Inst 2013;105:95-103.
55. Grote VA, Rohrmann S, Dossus L, et al. The association of circulating adiponectin levels with pancreatic cancer risk: a study within the prospective EPIC cohort. Int J Cancer 2012;130:2428-37.
56. Dimou NL, Papadimitriou N, Mariosa D, et al. CCFR. Circulating adipokine concentrations and risk of five obesity-related cancers: a mendelian randomization study. Int J Cancer 2021;148:1625-36.
57. Yang JP, Li X, Wang F, Gao M, Li SL, Chen KS. Association analysis of genetic variants of adiponectin gene and risk of pancreatic cancer. Int J Clin Exp Med 2015;8:8094-100.
58. Dalamaga M, Migdalis I, Fargnoli JL, et al. Pancreatic cancer expresses adiponectin receptors and is associated with hypoleptinemia and hyperadiponectinemia: a case-control study. Cancer Causes Control 2009;20:625-33.
59. Dranka-Bojarowska D, Lekstan A, Olakowski M et al. The assessment of serum concentration of adiponectin, leptin and serum carbohydrate antigen-19.9 in patients with pancreatic cancer and chronic pancreatitis. J Physiol Pharmaco 2015;66:653-63.
60. Eibl G, Rozengurt E. Obesity and pancreatic cancer: insight into mechanisms. Cancers (Basel) 2021;13:5067.
61. Messaggio F, Mendonsa AM, Castellanos J, et al. Adiponectin receptor agonists inhibit leptin induced pSTAT3 and in vivo pancreatic tumor growth. Oncotarget 2017;8:85378-91.
62. Kadri Colakoglu M, Bostanci EB, Ozdemir Y, et al. Roles of adiponectin and leptin as diagnostic markers in pancreatic cancer. Bratisl Lek Listy 2017;118:394-8.
63. Zyromski NJ, Mathur A, Pitt HA, et al. Obesity potentiates the growth and dissemination of pancreatic cancer. Surgery 2009;146:258-63.
64. Otvos L Jr. Potential adiponectin receptor response modifier therapeutics. Front Endocrinol (Lausanne) 2019;10:539.
65. Nigro E, Daniele A, Salzillo A, Ragone A, Naviglio S, Sapio L. AdipoRon and other adiponectin receptor agonists as potential candidates in cancer treatments. Int J Mol Sci 2021;22:5569.
66. Sapio L, Nigro E, Ragone A, et al. AdipoRon affects cell cycle progression and inhibits proliferation in human osteosarcoma cells. J Oncol 2020;2020:7262479.
67. Okada-Iwabu M, Yamauchi T, Iwabu M, et al. A small-molecule AdipoR agonist for type 2 diabetes and short life in obesity. Nature 2013;503:493-9.
68. Akimoto M, Maruyama R, Kawabata Y, Tajima Y, Takenaga K. Antidiabetic adiponectin receptor agonist AdipoRon suppresses tumour growth of pancreatic cancer by inducing RIPK1/ERK-dependent necroptosis. Cell Death Dis 2018;9:804.
69. Manley SJ, Olou AA, Jack JL, et al. Synthetic adiponectin-receptor agonist, AdipoRon, induces glycolytic dependence in pancreatic cancer cells. Cell Death Dis 2022;13:114.
70. Ragone A, Salzillo A, Spina A, Naviglio S, Sapio L. Integrating gemcitabine-based therapy with adiporon enhances growth inhibition in human PDAC cell lines. Front Pharmacol 2022;13:837503.
71. Takenaga K, Akimoto M, Koshikawa N, Nagase H. Obesity reduces the anticancer effect of AdipoRon against orthotopic pancreatic cancer in diet-induced obese mice. Sci Rep 2021;11:2923.
72. Latenstein AEJ, van der Geest LGM, Bonsing BA, et al. Dutch Pancreatic Cancer Group. Nationwide trends in incidence, treatment and survival of pancreatic ductal adenocarcinoma. Eur J Cancer 2020;125:83-93.
73. Mucciolo G, Roux C, Scagliotti A, Brugiapaglia S, Novelli F, Cappello P. The dark side of immunotherapy: pancreatic cancer. Cancer Drug Resist 2020;3:491-520.
74. Elsayed M, Abdelrahim M. The latest advancement in pancreatic ductal adenocarcinoma therapy: a review article for the latest guidelines and novel therapies. Biomedicines 2021;9:389.
75. Blomstrand H, Scheibling U, Bratthäll C, Green H, Elander NO. Real world evidence on gemcitabine and nab-paclitaxel combination chemotherapy in advanced pancreatic cancer. BMC Cancer 2019;19:40.
76. Hoyer K, Hablesreiter R, Inoue Y, et al. A genetically defined signature of responsiveness to erlotinib in early-stage pancreatic cancer patients: results from the CONKO-005 trial. EBioMedicine 2021;66:103327.
77. Santofimia-Castaño P, Iovanna J. Combating pancreatic cancer chemoresistance by triggering multiple cell death pathways. Pancreatology 2021;21:522-9.
78. Viale A, Pettazzoni P, Lyssiotis CA, et al. Oncogene ablation-resistant pancreatic cancer cells depend on mitochondrial function. Nature 2014;514:628-32.
79. Peng J, Cui Y, Xu S, et al. Altered glycolysis results in drug-resistant in clinical tumor therapy. Oncol Lett 2021;21:369.
80. Li Petri G, El Hassouni B, Sciarrillo R, et al. Impact of hypoxia on chemoresistance of mesothelioma mediated by the proton-coupled folate transporter, and preclinical activity of new anti-LDH-A compounds. Br J Cancer 2020;123:644-56.
81. Hassouni BE, Franczak M, Capula M, et al. Lactate dehydrogenase A inhibition by small molecular entities: steps in the right direction. Oncoscience 2020;7:76-80.
82. Matsuura F, Oku H, Koseki M, et al. Adiponectin accelerates reverse cholesterol transport by increasing high density lipoprotein assembly in the liver. Biochem Biophys Res Commun 2007;358:1091-5.
