Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA: A Cancer J Clin. 2023;73(1):17–48.
Wood LD, Canto MI, Jaffee EM, Simeone DM. Pancreatic cancer: pathogenesis, screening, diagnosis, and treatment. Gastroenterology. 2022;163(2):386–402.e1.
Carreras-Torres R, Johansson M, Gaborieau V, Haycock PC, Wade KH, Relton CL, et al. The role of obesity, type 2 diabetes, and metabolic factors in pancreatic cancer: a Mendelian randomization study. J Nl Cancer Inst. 2017;109(9).
Jin X, Qiu T, Li L, Yu R, Chen X, Li C, et al. Pathophysiology of obesity and its associated diseases. Acta Pharm Sin B. 2023;13(6):2403–24.
Khandekar MJ, Cohen P, Spiegelman BM. Molecular mechanisms of cancer development in obesity. Nat Rev Cancer. 2011;11(12):886–95.
Klein AP. Pancreatic cancer epidemiology: understanding the role of lifestyle and inherited risk factors. Nat Rev Gastroenterol Hepatol. 2021;18(7):493–502.
Maitra A, Sharma A, Brand RE, Van Den Eeden SK, Fisher WE, Hart PA, et al. A Prospective Study to Establish a New-Onset Diabetes Cohort: From the Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer. Pancreas. 2018;47(10):1244–8.
Araki T, Nagashima M, Hirasawa H, Tamalu F, Katagiri Y, Miwa N. Epigenome-wide association analysis of pancreatic exocrine cells from high-fat- and normal diet-fed mice and its potential use for understanding the oncogenesis of human pancreatic cancer. Biochem Biophys Res Commun. 2022;637:50–7.
Cascetta P, Cavaliere A, Piro G, Torroni L, Santoro R, Tortora G, et al. Pancreatic cancer and obesity: molecular mechanisms of cell transformation and chemoresistance. Int J Mol Sci. 2018;19(11).
Wlodarczyk M, Nowicka G. Obesity, DNA damage, and development of obesity-related diseases. Int J Mol Sci. 2019;20(5).
Pavlova NN, Zhu J, Thompson CB. The hallmarks of cancer metabolism: still emerging. Cell Metab. 2022;34(3):355–77.
Kohli RM, Zhang Y. TET enzymes, TDG and the dynamics of DNA demethylation. Nature. 2013;502(7472):472–9.
Jones PA, Baylin SB. The fundamental role of epigenetic events in cancer. Nat Rev Genet. 2002;3(6):415–28.
Patil V, Ward RL, Hesson LB. The evidence for functional non-CpG methylation in mammalian cells. Epigenetics. 2014;9(6):823–8.
Tahiliani M, Koh KP, Shen Y, Pastor WA, Bandukwala H, Brudno Y, et al. Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science. 2009;324(5929):930–5.
Vasovcak P, Krepelova A, Menigatti M, Puchmajerova A, Skapa P, Augustinakova A, et al. Unique mutational profile associated with a loss of TDG expression in the rectal cancer of a patient with a constitutional PMS2 deficiency. DNA Repair. 2012;11(7):616–23.
Wiebauer K, Jiricny J. Mismatch-specific thymine DNA glycosylase and DNA polymerase beta mediate the correction of G.T mispairs in nuclear extracts from human cells. Proc Natl Acad Sci USA. 1990;87(15):5842–5.
Gohil D, Sarker AH, Roy R. Base excision repair: mechanisms and impact in biology, disease, and medicine. Int J Mol Sci. 2023;24(18).
Sun L, Zhang H, Gao P. Metabolic reprogramming and epigenetic modifications on the path to cancer. Protein cell. 2022;13(12):877–919.
Wang P, Chen LL, Xiong Y, Ye D. Metabolite regulation of epigenetics in cancer. Cell Rep. 2024;43(10):114815.
Spallotta F, Cencioni C, Atlante S, Garella D, Cocco M, Mori M, et al. Stable oxidative cytosine modifications accumulate in cardiac mesenchymal cells from type2 diabetes patients: rescue by alpha-ketoglutarate and TET-TDG functional reactivation. Circ Res. 2018;122(1):31–46.
Mancuso P, Tricarico R, Bhattacharjee V, Cosentino L, Kadariya Y, Jelinek J, et al. Correction to: Thymine DNA glycosylase as a novel target for melanoma. Oncogene. 2022;41(23):3300–1.
Wang G, Rao P. Succinate dehydrogenase-deficient renal cell carcinoma: a short review. Arch Pathol Lab Med. 2018;142(10):1284–8.
Xu H, Long S, Xu C, Li Z, Chen J, Yang B, et al. TNC upregulation promotes glioma tumourigenesis through TDG-mediated active DNA demethylation. Cell Death Discov. 2024;10(1):347.
Bracci PM. Obesity and pancreatic cancer: overview of epidemiologic evidence and biologic mechanisms. Mol Carcinog. 2012;51(1):53–63.
Ariston Gabriel AN, Jiao Q, Yvette U, Yang X, Al-Ameri SA, Du L, et al. Differences between KC and KPC pancreatic ductal adenocarcinoma mice models, in terms of their modeling biology and their clinical relevance. Pancreatology. 2020;20(1):79–88.
Geeraerts SL, Heylen E, De Keersmaecker K, Kampen KR. The ins and outs of serine and glycine metabolism in cancer. Nat Metab. 2021;3(2):131–41.
Zeng JD, Wu WKK, Wang HY, Li XX. Serine and one-carbon metabolism, a bridge that links mTOR signaling and DNA methylation in cancer. Pharmacol Res. 2019;149:104352.
Lu X, Han D, Zhao BS, Song CX, Zhang LS, Dore LC, et al. Base-resolution maps of 5-formylcytosine and 5-carboxylcytosine reveal genome-wide DNA demethylation dynamics. Cell Res. 2015;25(3):386–9.
Raiber EA, Murat P, Chirgadze DY, Beraldi D, Luisi BF, Balasubramanian S. 5-Formylcytosine alters the structure of the DNA double helix. Nat Struct Mol Biol. 2015;22(1):44–9.
Apte MV, Wilson JS, Lugea A, Pandol SJ. A starring role for stellate cells in the pancreatic cancer microenvironment. Gastroenterology. 2013;144(6):1210–9.
Letouze E, Martinelli C, Loriot C, Burnichon N, Abermil N, Ottolenghi C, et al. SDH mutations establish a hypermethylator phenotype in paraganglioma. Cancer Cell. 2013;23(6):739–52.
Malik SS, Coey CT, Varney KM, Pozharski E, Drohat AC. Thymine DNA glycosylase exhibits negligible affinity for nucleobases that it removes from DNA. Nucleic Acids Res. 2015;43(19):9541–52.
Chen D, Lucey MJ, Phoenix F, Lopez-Garcia J, Hart SM, Losson R, et al. T:G mismatch-specific thymine-DNA glycosylase potentiates transcription of estrogen-regulated genes through direct interaction with estrogen receptor alpha. J Biol Chem. 2003;278(40):38586–92.
Wilson DM 3rd, Barsky D. The major human abasic endonuclease: formation, consequences and repair of abasic lesions in DNA. Mutat Res. 2001;485(4):283–307.
Tomkinson AE, Howes TR, Wiest NE. DNA ligases as therapeutic targets. Transl Cancer Res. 2013;2(3).
Pandey S, Anang V, Schumacher MM. Mitochondria driven innate immune signaling and inflammation in cancer growth, immune evasion, and therapeutic resistance. Int Rev Cell Mol Biol. 2024;386:223–47.
Chari ST, Wu B, Lopez C, Lustigova E, Chen Q, Van Den Eeden SK, et al. Risk of pancreatic cancer in glycemically defined new-onset diabetes: a prospective cohort study. Gastroenterology. 2025.
Sah RP, Sharma A, Nagpal S, Patlolla SH, Sharma A, Kandlakunta H, et al. Phases of metabolic and soft tissue changes in months preceding a diagnosis of pancreatic ductal adenocarcinoma. Gastroenterology. 2019;156(6):1742–52.
Sharma A, Smyrk TC, Levy MJ, Topazian MA, Chari ST. Fasting blood glucose levels provide estimate of duration and progression of pancreatic cancer before diagnosis. Gastroenterology. 2018;155(2):490–500.e2.
Gumpper-Fedus K, Hart PA, Belury MA, Crowe O, Cole RM, Pita Grisanti V, et al. Altered plasma fatty acid abundance is associated with cachexia in treatment-naive pancreatic cancer. Cells. 2022;11(5).
Morris, JPt, Yashinskie JJ, Koche R, Chandwani R, Tian S, Chen CC, et al. alpha-Ketoglutarate links p53 to cell fate during tumour suppression. Nature. 2019;573(7775):595–9.
Atallah R, Olschewski A, Heinemann A. Succinate at the crossroad of metabolism and angiogenesis: roles of SDH, HIF1alpha and SUCNR1. Biomedicines. 2022;10(12).
Laukka T, Mariani CJ, Ihantola T, Cao JZ, Hokkanen J, Kaelin WG Jr, et al. Fumarate and succinate regulate expression of hypoxia-inducible genes via TET enzymes. J Biol Chem. 2016;291(8):4256–65.
Selak MA, Armour SM, MacKenzie ED, Boulahbel H, Watson DG, Mansfield KD, et al. Succinate links TCA cycle dysfunction to oncogenesis by inhibiting HIF-alpha prolyl hydroxylase. Cancer Cell. 2005;7(1):77–85.
Zhang W, Lang R. Succinate metabolism: a promising therapeutic target for inflammation, ischemia/reperfusion injury and cancer. Front Cell Dev Biol. 2023;11:1266973.
Das PM, Singal R. DNA methylation and cancer. J Clin Oncol. 2004;22(22):4632–42.
Tan AC, Jimeno A, Lin SH, Wheelhouse J, Chan F, Solomon A, et al. Characterizing DNA methylation patterns in pancreatic cancer genome. Mol Oncol. 2009;3(5-6):425–38.
Ueki T, Toyota M, Sohn T, Yeo CJ, Issa JP, Hruban RH, et al. Hypermethylation of multiple genes in pancreatic adenocarcinoma. Cancer Res. 2000;60(7):1835–9.
Luo L, Fu S, Du W, He LN, Zhang X, Wang Y, et al. LRRC3B and its promoter hypomethylation status predicts response to anti-PD-1 based immunotherapy. Front Immunol. 2023;14:959868.
Atlante S, Visintin A, Marini E, Savoia M, Dianzani C, Giorgis M, et al. alpha-ketoglutarate dehydrogenase inhibition counteracts breast cancer-associated lung metastasis. Cell Death Dis. 2018;9(7):756.
Huang Y, Wang G, Liang Z, Yang Y, Cui L, Liu CY. Loss of nuclear localization of TET2 in colorectal cancer. Clin Epigenet. 2016;8:9.
Muller T, Gessi M, Waha A, Isselstein LJ, Luxen D, Freihoff D, et al. Nuclear exclusion of TET1 is associated with loss of 5-hydroxymethylcytosine in IDH1 wild-type gliomas. Am J Pathol. 2012;181(2):675–83.
Xu X, Yu T, Shi J, Chen X, Zhang W, Lin T, et al. Thymine DNA glycosylase is a positive regulator of Wnt signaling in colorectal cancer. J Biol Chem. 2014;289(13):8881–90.
Xu X, Watt DS, Liu C. Multifaceted roles for thymine DNA glycosylase in embryonic development and human carcinogenesis. Acta Biochim Biophys Sin. 2016;48(1):82–9.
Zhou W, Zhang L, Chen P, Li S, Cheng Y. Thymine DNA glycosylase-regulated TAZ promotes radioresistance by targeting nonhomologous end joining and tumor progression in esophageal cancer. Cancer Sci. 2020;111(10):3613–25.
Nowsheen S, Wukovich RL, Aziz K, Kalogerinis PT, Richardson CC, Panayiotidis MI, et al. Accumulation of oxidatively induced clustered DNA lesions in human tumor tissues. Mutat Res. 2009;674(1-2):131–6.
Wei S, Perera MLW, Sakhtemani R, Bhagwat AS. A novel class of chemicals that react with abasic sites in DNA and specifically kill B cell cancers. PloS one. 2017;12(9):e0185010.
Tong J, Song J, Zhang W, Zhai J, Guan Q, Wang H, et al. When DNA-damage responses meet innate and adaptive immunity. Cell Mol Life Sci. 2024;81(1):185.
de Latouliere L, Manni I, Iacobini C, Pugliese G, Grazi GL, Perri P, et al. A bioluminescent mouse model of proliferation to highlight early stages of pancreatic cancer: a suitable tool for preclinical studies. Ann Anat = Anatomischer Anz. 2016;207:2–8.
Pettersson US, Walden TB, Carlsson PO, Jansson L, Phillipson M. Female mice are protected against high-fat diet induced metabolic syndrome and increase the regulatory T cell population in adipose tissue. PloS One. 2012;7(9):e46057.
Siddiqui I, Erreni M, Kamal MA, Porta C, Marchesi F, Pesce S, et al. Differential role of Interleukin-1 and Interleukin-6 in K-Ras-driven pancreatic carcinoma undergoing mesenchymal transition. Oncoimmunology. 2018;7(2):e1388485.
Middonti E, Astanina E, Vallariello E, Hoza RM, Metovic J, Spadi R, et al. A neuroligin-2-YAP axis regulates progression of pancreatic intraepithelial neoplasia. EMBO Rep. 2024;25(4):1886–908.
Adler J, Parmryd I. Quantifying colocalization by correlation: the Pearson correlation coefficient is superior to the Mander’s overlap coefficient. Cytom Part A. 2010;77(8):733–42.
Humbert N, Kovalenko L, Saladini F, Giannini A, Pires M, Botzanowski T, et al. Thia)calixarenephosphonic acids as potent inhibitors of the nucleic acid chaperone activity of the HIV-1 nucleocapsid protein with a new binding mode and multitarget antiviral activity. ACS Infect Dis. 2020;6(4):687–702.
Tian C, Kasavajhala K, Belfon KAA, Raguette L, Huang H, Migues AN, et al. ff19SB: amino-acid-specific protein backbone parameters trained against quantum mechanics energy surfaces in solution. J Chem Theory Comput. 2020;16(1):528–52.
Wang J, Wolf RM, Caldwell JW, Kollman PA, Case DA. Development and testing of a general amber force field. J Comput Chem. 2004;25(9):1157–74.
Rubenstein AB, Blacklock K, Nguyen H, Case DA, Khare SD. Systematic comparison of amber and rosetta energy functions for protein structure evaluation. J Chem Theory Comput. 2018;14(11):6015–25.
Roe DR, Cheatham TE 3rd. PTRAJ and CPPTRAJ: software for processing and analysis of molecular dynamics trajectory data. J Chem Theory Comput. 2013;9(7):3084–95.
Cipolla L, Bertoletti F, Maffia A, Liang CC, Lehmann AR, Cohn MA, et al. UBR5 interacts with the replication fork and protects DNA replication from DNA polymerase eta toxicity. Nucleic Acids Res. 2019;47(21):11268–83.
