REFERENCES
1. Robertson BM, Fane ME, Weeraratna AT, Rebecca VW. Determinants of resistance and response to melanoma therapy. Nat Cancer. 2024;5:964-82.
2. Shang Y, Cao T, Li J, et al. BRAF inhibitor resistance in melanoma: from resistance mechanisms to therapeutic innovations. Mol Biomed. 2026;7:27.
3. Hamis S, Browning AP, Jenner AL, Villa C, Maini PK, Cassidy T. Growth rate-driven modelling suggests that phenotypic adaptation drives drug resistance in BRAFV600E-mutant melanoma. Commun Biol. 2026;9:385.
4. Rubanov A, Berico P, Hernando E. Epigenetic mechanisms underlying melanoma resistance to immune and targeted therapies. Cancers. 2022;14:5858.
5. Cai M, Wang L, Yang W, Niu J. Breaking barriers: epithelial-mesenchymal transition role in melanoma invasion and resistance. Melanoma Res. 2026;36:1-15.
6. Zhang X, Zhang Y, Wang C, Wang X. TET (Ten-eleven translocation) family proteins: structure, biological functions and applications. Signal Transduct Target Ther. 2023;8:297.
7. Kharat SS, Sharan SK. 5-Hydroxymethylcytosine: a key epigenetic mark in cancer and chemotherapy response. Epigenetics Chromatin. 2025;18:73.
8. Aanniz T, El Fessikh M, Touhtouh J, et al. TET enzymes: involvement in cancer development and therapeutical perspectives. Biochim Biophys Acta Gene Regul Mech. 2025;1868:195118.
9. Smith-Díaz CC, Das AB, Jurkowski TP, Hore TA, Vissers MCM. Exploring the ascorbate requirement of the 2-oxoglutarate-dependent dioxygenases. J Med Chem. 2025;68:2219-37.
10. Giansanti M, Karimi T, Faraoni I, Graziani G. High-dose vitamin C: preclinical evidence for tailoring treatment in cancer patients. Cancers. 2021;13:1428.
11. Lian CG, Xu Y, Ceol C, et al. Loss of 5-hydroxymethylcytosine is an epigenetic hallmark of melanoma. Cell. 2012;150:1135-46.
12. Saldanha G, Joshi K, Lawes K, et al. 5-Hydroxymethylcytosine is an independent predictor of survival in malignant melanoma. Mod Pathol. 2017;30:60-8.
13. Fischer GM, Fang R, Xu S, et al. Loss of ten-eleven translocation 2 (TET2) facilitates aggressive behaviour in cutaneous melanoma by inducing peroxisome proliferator-activated receptor-γ coactivator 1α expression and oxidative phosphorylation. Br J Dermatol. 2026;194:111-24.
14. Bonvin E, Radaelli E, Bizet M, et al. TET2-dependent hydroxymethylome plasticity reduces melanoma initiation and progression. Cancer Res. 2019;79:482-94.
15. Ruffini F, Ceci C, Atzori MG, et al. Targeting of PDGF-C/NRP-1 autocrine loop as a new strategy for counteracting the invasiveness of melanoma resistant to braf inhibitors. Pharmacol Res. 2023;192:106782.
16. Caporali S, Alvino E, Lacal PM, et al. Targeting the PI3K/AKT/mTOR pathway overcomes the stimulating effect of dabrafenib on the invasive behavior of melanoma cells with acquired resistance to the BRAF inhibitor. Int J Oncol. 2016;49:1164-74.
17. Kang Y, Ji Z, Li H, Tsao H. Divergent BRAF inhibitor resistance mechanisms revealed through epigenetic mapping. J Invest Dermatol. 2023;143:842-53.e6.
18. Tang Z, Kang B, Li C, Chen T, Zhang Z. GEPIA2: an enhanced web server for large-scale expression profiling and interactive analysis. Nucleic Acids Res. 2019;47:W556-60.
19. Minor EA, Court BL, Young JI, Wang G. Ascorbate induces ten-eleven translocation (Tet) methylcytosine dioxygenase-mediated generation of 5-hydroxymethylcytosine. J Biol Chem. 2013;288:13669-74.
20. Gawronski M, Starczak M, Wasilow A, Dziaman T, Olinski R, Gackowski D. Loss of TET2 activity limits the ability of vitamin C to activate DNA demethylation in human HAP1 cells. Epigenetics Chromatin. 2025;18:76.
21. Chen Q, Espey MG, Sun AY, et al. Pharmacologic doses of ascorbate act as a prooxidant and decrease growth of aggressive tumor xenografts in mice. Proc Natl Acad Sci U S A. 2008;105:11105-9.
22. Sinnberg T, Noor S, Venturelli S, et al. The ROS-induced cytotoxicity of ascorbate is attenuated by hypoxia and HIF-1alpha in the NCI60 cancer cell lines. J Cell Mol Med. 2014;18:530-41.
23. Cisternas P, Silva-Alvarez C, Martínez F, et al. The oxidized form of vitamin C, dehydroascorbic acid, regulates neuronal energy metabolism. J Neurochem. 2014;129:663-71.
24. Villagrán M, Burgos CF, Rivas CI, Mardones L. Identification of structural determinants of the transport of the dehydroascorbic acid mediated by glucose transport GLUT1. Molecules. 2023;28:521.
25. Gerecke C, Schumacher F, Edlich A, et al. Vitamin C promotes decitabine or azacytidine induced DNA hydroxymethylation and subsequent reactivation of the epigenetically silenced tumour suppressor CDKN1A in colon cancer cells. Oncotarget. 2018;9:32822-40.
26. Kharat SS, Mishra AP, Sengodan SK, et al. 5hmC enhances PARP trapping and restores PARP inhibitor sensitivity in chemoresistant BRCA1/2-deficient cells. J Biol Chem. 2025;301:110393.
27. Giansanti M, De Gabrieli A, Prete SP, et al. Poly(ADP-ribose) polymerase inhibitors for arsenic trioxide-resistant acute promyelocytic leukemia: synergistic in vitro antitumor effects with hypomethylating agents or high-dose vitamin C. J Pharmacol Exp Ther. 2021;377:385-97.
28. Vashisht Gopal YN, Gammon S, Prasad R, et al. A novel mitochondrial inhibitor blocks MAPK pathway and overcomes MAPK inhibitor resistance in melanoma. Clin Cancer Res. 2019;25:6429-42.
29. Borbényi-Galambos K, Erdélyi K, Ditrói T, et al. Realigned transsulfuration drives BRAF-V600E-targeted therapy resistance in melanoma. Cell Metab. 2025;37:1171-88.e9.
30. Khamari R, Trinh A, Gabert PE, et al. Glucose metabolism and NRF2 coordinate the antioxidant response in melanoma resistant to MAPK inhibitors. Cell Death Dis. 2018;9:325.
31. Leesang TE, Brabson JP, Yap YS, et al. Retinoic acid and ascorbate synergize to suppress myeloid leukemia via TET2 activation. Cell Rep. 2025;44:116379.
32. Guan Y, Greenberg EF, Hasipek M, et al. Context dependent effects of ascorbic acid treatment in TET2 mutant myeloid neoplasia. Commun Biol. 2020;3:493.
33. Montel-Hagen A, Kinet S, Manel N, et al. Erythrocyte Glut1 triggers dehydroascorbic acid uptake in mammals unable to synthesize vitamin C. Cell. 2008;132:1039-48.
34. Rumsey SC, Kwon O, Xu GW, Burant CF, Simpson I, Levine M. Glucose transporter isoforms GLUT1 and GLUT3 transport dehydroascorbic acid. J Biol Chem. 1997;272:18982-9.
35. Lu YX, Wu QN, Chen DL, et al. Pharmacological ascorbate suppresses growth of gastric cancer cells with GLUT1 overexpression and enhances the efficacy of oxaliplatin through redox modulation. Theranostics. 2018;8:1312-26.
36. Yuan L, Mishra R, Patel H, et al. BRAF mutant melanoma adjusts to BRAF/MEK inhibitors via dependence on increased antioxidant SOD2 and increased reactive oxygen species levels. Cancers. 2020;12:1661.
37. Villagran M, Ferreira J, Martorell M, Mardones L. The role of vitamin C in cancer prevention and therapy: a literature review. Antioxidants. 2021;10:1894.
