REFERENCES

1. Zhou K, Liu Y, Tang C, Zhu H. Pancreatic cancer: pathogenesis and clinical studies. MedComm. 2025;6:e70162.

2. Orth M, Metzger P, Gerum S, et al. Pancreatic ductal adenocarcinoma: biological hallmarks, current status, and future perspectives of combined modality treatment approaches. Radiat Oncol. 2019;14:141.

3. National Cancer Institute. SEER Cancer stat facts: pancreatic cancer. 2026. Available from: https://seer.cancer.gov/statfacts/html/pancreas.html. [Last accessed on 21 Aug 2026].

4. Sarantis P, Koustas E, Papadimitropoulou A, Papavassiliou AG, Karamouzis MV. Pancreatic ductal adenocarcinoma: treatment hurdles, tumor microenvironment and immunotherapy. World J Gastrointest Oncol. 2020;12:173-81.

5. Sun Y, Jiang W, Liao X, Wang D. Hallmarks of perineural invasion in pancreatic ductal adenocarcinoma: new biological dimensions. Front Oncol. 2024;14:1421067.

6. Encarnación-Rosado J, Kimmelman AC. Harnessing metabolic dependencies in pancreatic cancers. Nat Rev Gastroenterol Hepatol. 2021;18:482-92.

7. Liu WW, Zheng SQ, Li T, et al. RNA modifications in cellular metabolism: implications for metabolism-targeted therapy and immunotherapy. Signal Transduct Target Ther. 2024;9:70.

8. Mastrogiorgio G, Macchiaiolo M, Buonuomo PS, et al. Clinical and molecular characterization of patients with adenylosuccinate lyase deficiency. Orphanet J Rare Dis. 2021;16:112.

9. Hsu TW, Wang WY, Chen A, et al. Nrf2-mediated adenylosuccinate lyase promotes resistance to gemcitabine in pancreatic ductal adenocarcinoma cells through ferroptosis escape. J Cell Physiol. 2024;239:e31416.

10. Arnold PK, Finley LWS. Regulation and function of the mammalian tricarboxylic acid cycle. J Biol Chem. 2023;299:102838.

11. Mullen NJ, Singh PK. Nucleotide metabolism: a pan-cancer metabolic dependency. Nat Rev Cancer. 2023;23:275-94.

12. Ali ES, Ben-Sahra I. Regulation of nucleotide metabolism in cancers and immune disorders. Trends Cell Biol. 2023;33:950-66.

13. Duan Y, Hu Z, Han P, et al. ADSL-generated fumarate binds and inhibits STING to promote tumour immune evasion. Nat Cell Biol. 2025;27:668-82.

14. Liao J, Song Q, Li J, et al. Carcinogenic effect of adenylosuccinate lyase (ADSL) in prostate cancer development and progression through the cell cycle pathway. Cancer Cell Int. 2021;21:467.

15. Jiang T, Sánchez-Rivera FJ, Soto-Feliciano YM, et al. Targeting the de novo purine synthesis pathway through adenylosuccinate lyase depletion impairs liver cancer growth by perturbing mitochondrial function. Hepatology. 2021;74:233-47.

16. Taha-Mehlitz S, Bianco G, Coto-Llerena M, et al. Adenylosuccinate lyase is oncogenic in colorectal cancer by causing mitochondrial dysfunction and independent activation of NRF2 and mTOR-MYC-axis. Theranostics. 2021;11:4011-29.

17. Keller KE, Tan IS, Lee YS. SAICAR stimulates pyruvate kinase isoform M2 and promotes cancer cell survival in glucose-limited conditions. Science. 2012;338:1069-72.

18. Toth EA, Yeates TO. The structure of adenylosuccinate lyase, an enzyme with dual activity in the de novo purine biosynthetic pathway. Structure. 2000;8:163-74.

19. Souckova O, Skopova V, Baresova V, et al. Metabolites of de novo purine synthesis: metabolic regulators and cytotoxic compounds. Metabolites. 2022;12:1210.

20. Wu H, Fu M, Wu M, Cao Z, Zhang Q, Liu Z. Emerging mechanisms and promising approaches in pancreatic cancer metabolism. Cell Death Dis. 2024;15:553.

21. Grasso C, Jansen G, Giovannetti E. Drug resistance in pancreatic cancer: impact of altered energy metabolism. Crit Rev Oncol Hematol. 2017;114:139-52.

22. Park H, Ohshima K, Nojima S, et al. Adenylosuccinate lyase enhances aggressiveness of endometrial cancer by increasing killer cell lectin-like receptor C3 expression by fumarate. Lab Invest. 2018;98:449-61.

23. Van Laer B, Kapp U, Soler-Lopez M, et al. Molecular comparison of Neanderthal and Modern Human adenylosuccinate lyase. Sci Rep. 2018;8:18008.

24. Ray SP, Deaton MK, Capodagli GC, et al. Structural and biochemical characterization of human adenylosuccinate lyase (ADSL) and the R303C ADSL deficiency-associated mutation. Biochemistry. 2012;51:6701-13.

25. Andelman-Gur MM, Saitsu H, Matsumoto N, et al. Myoclonic tremor status as a presenting symptom of adenylosuccinate lyase deficiency. Eur J Med Genet. 2020;63:104061.

26. Fenton AR, Janowitz HN, Franklin LP, et al. A Caenorhabditis elegans model of adenylosuccinate lyase deficiency reveals neuromuscular and reproductive phenotypes of distinct etiology. Mol Genet Metab. 2023;140:107686.

27. Jurecka A, Zikanova M, Kmoch S, Tylki-Szymańska A. Adenylosuccinate lyase deficiency. J Inherit Metab Dis. 2015;38:231-42.

28. Macchiaiolo M, Buonuomo PS, Mastrogiorgio G, et al. Very mild isolated intellectual disability caused by adenylosuccinate lyase deficiency: a new phenotype. Mol Genet Metab Rep. 2020;23:100592.

29. Zhu XG, Chudnovskiy A, Baudrier L, et al. Functional genomics in vivo reveal metabolic dependencies of pancreatic cancer cells. Cell Metab. 2021;33:211-21.e6.

30. Valizadeh Osalo M, Hosseini P, Charkhian H, Soltanzadeh H, Goharkhany S, Tuncer SB. The prevalence of ADSL (rs3788579) and CYP1A2 (rs17861162) polymorphisms in female breast cancer patients in North-West Iran. Discov Oncol. 2024;15:59.

31. Zurlo G, Zhang Q. Adenylosuccinate lyase hydroxylation contributes to triple negative breast cancer via the activation of cMYC. Mol Cell Oncol. 2020;7:1707045.

32. Zhang WC, Skiados N, Aftab F, et al. MicroRNA-21 guide and passenger strand regulation of adenylosuccinate lyase-mediated purine metabolism promotes transition to an EGFR-TKI-tolerant persister state. Cancer Gene Ther. 2022;29:1878-94.

33. Hsieh AL, Walton ZE, Altman BJ, Stine ZE, Dang CV. MYC and metabolism on the path to cancer. Semin Cell Dev Biol. 2015;43:11-21.

34. Zhou Y, Gao X, Yuan M, Yang B, He Q, Cao J. Targeting Myc interacting proteins as a winding path in cancer therapy. Front Pharmacol. 2021;12:748852.

35. Halbrook CJ, Lyssiotis CA, Pasca di Magliano M, Maitra A. Pancreatic cancer: advances and challenges. Cell. 2023;186:1729-54.

36. Xiao M, Yang H, Xu W, et al. Inhibition of α-KG-dependent histone and DNA demethylases by fumarate and succinate that are accumulated in mutations of FH and SDH tumor suppressors. Genes Dev. 2012;26:1326-38.

37. Robinson BW, Im MM, Ljungman M, Praz F, Shewach DS. Enhanced radiosensitization with gemcitabine in mismatch repair-deficient HCT116 cells. Cancer Res. 2003;63:6935-41.

38. Bergman AM, Pinedo HM, Peters GJ. Determinants of resistance to 2',2'-difluorodeoxycytidine (gemcitabine). Drug Resist Updat. 2002;5:19-33.

39. Ruiz van Haperen VW, Veerman G, Boven E, Noordhuis P, Vermorken JB, Peters GJ. Schedule dependence of sensitivity to 2',2'-difluorodeoxycytidine (Gemcitabine) in relation to accumulation and retention of its triphosphate in solid tumour cell lines and solid tumours. Biochem Pharmacol. 1994;48:1327-39.

40. Van Moorsel CJ, Smid K, Voorn DA, Bergman AM, Pinedo HM, Peters GJ. Effect of gemcitabine and cis-platinum combinations on ribonucleotide and deoxyribonucleotide pools in ovarian cancer cell lines. Int J Oncol. 2003;22:201-7.

41. van Moorsel CJ, Bergman AM, Veerman G, et al. Differential effects of gemcitabine on ribonucleotide pools of twenty-one solid tumour and leukaemia cell lines. Biochim Biophys Acta. 2000;1474:5-12.

42. Shewach DS, Hahn TM, Chang E, Hertel LW, Lawrence TS. Metabolism of 2',2'-difluoro-2'-deoxycytidine and radiation sensitization of human colon carcinoma cells. Cancer Res. 1994;54:3218-23.

43. Shewach DS, Reynolds KK, Hertel L. Nucleotide specificity of human deoxycytidine kinase. Mol Pharmacol. 1992;42:518-24.

44. Tesei A, Ricotti L, De Paola F, Amadori D, Frassineti GL, Zoli W. In vitro schedule-dependent interactions between the multitargeted antifolate LY231514 and gemcitabine in human colon adenocarcinoma cell lines. Clin Cancer Res. 2002;8:233-9.

45. Giovannetti E, Mey V, Danesi R, Mosca I, Del Tacca M. Synergistic cytotoxicity and pharmacogenetics of gemcitabine and pemetrexed combination in pancreatic cancer cell lines. Clin Cancer Res. 2004;10:2936-43.

46. Koltai T, Reshkin SJ, Carvalho TMA, et al. Resistance to gemcitabine in pancreatic ductal adenocarcinoma: a physiopathologic and pharmacologic review. Cancers. 2022;14:2486.

47. Höfer S, Frasch L, Brajkovic S, et al. Gemcitabine and ATR inhibitors synergize to kill PDAC cells by blocking DNA damage response. Mol Syst Biol. 2025;21:231-53.

48. Jiang X, Stockwell BR, Conrad M. Ferroptosis: mechanisms, biology and role in disease. Nat Rev Mol Cell Biol. 2021;22:266-82.

49. He F, Ru X, Wen T. NRF2, a transcription factor for stress response and beyond. Int J Mol Sci. 2020;21:4777.

50. Kindler HL, Burris HA 3rd, Sandler AB, Oliff IA. A phase II multicenter study of L-alanosine, a potent inhibitor of adenine biosynthesis, in patients with MTAP-deficient cancer. Invest New Drugs. 2009;27:75-81.

51. Li Y, Du Y, Li R, et al. Spatial transcriptomics in pancreatic cancer: advances, prospects and challenges. Crit Rev Oncol Hematol. 2024;203:104430.

52. Shenoy A, Yousif A, Hussain MD. Recent advances and challenges in the treatment of advanced pancreatic cancer: an update on completed and ongoing clinical trials. Cancers. 2025;17:1319.

53. Purines 2018 basic and translational science on purinergic signaling and its components for a healthy and better world. Purinergic Signal. 2018;14:1-122.

54. Ali ES, Sahu U, Villa E, et al. ERK2 phosphorylates PFAS to mediate posttranslational control of de novo purine synthesis. Mol Cell. 2020;78:1178-91.e6.

55. Tran DH, Kim D, Kesavan R, et al. De novo and salvage purine synthesis pathways across tissues and tumors. Cell. 2024;187:3602-18.e20.

56. Stine ZE, Schug ZT, Salvino JM, Dang CV. Targeting cancer metabolism in the era of precision oncology. Nat Rev Drug Discov. 2022;21:141-62.

57. Ding M, Ma C, Lin Y, et al. Therapeutic targeting de novo purine biosynthesis driven by β-catenin-dependent PPAT upregulation in hepatoblastoma. Cell Death Dis. 2025;16:179.

58. Sharma MF, Firestine SM. Carboxylation in de novo purine biosynthesis. Methods Enzymol. 2024;708:389-424.

59. Donati G, Amati B. MYC and therapy resistance in cancer: risks and opportunities. Mol Oncol. 2022;16:3828-54.

60. Zheng P, Lin Z, Ding Y, Duan S. Targeting the dynamics of cancer metabolism in the era of precision oncology. Metabolism. 2023;145:155615.

61. Yabushita T, Goyama S. Nucleic acid metabolism: the key therapeutic target for myeloid tumors. Exp Hematol. 2025;142:104693.

62. Tabata S, Umemura S, Narita M, et al. Metabolic hallmarks for purine nucleotide biosynthesis in small cell lung carcinoma. Mol Cancer Res. 2024;22:82-93.

63. Tang S, Kapoor E, Ding L, et al. Effect of tocopherol conjugation on polycation-mediated siRNA delivery to orthotopic pancreatic tumors. Biomater Adv. 2023;145:213236.

64. Burks J, Nadella S, Mahmud A, et al. Cholecystokinin receptor-targeted polyplex nanoparticle inhibits growth and metastasis of pancreatic cancer. Cell Mol Gastroenterol Hepatol. 2018;6:17-32.

Cancer Drug Resistance
ISSN 2578-532X (Online)

Portico

All published articles will preserved here permanently:

https://www.portico.org/publishers/oae/

Portico

All published articles will preserved here permanently:

https://www.portico.org/publishers/oae/