1 J. Stubbe, W.A. van der DonkRibonucleotide reductases: radical enzymes with suicidal tendencies Chem Biol, 2 (12) (1995), pp. 793-801

2 P. ReichardFrom RNA to DNA, why so many ribonucleotide reductases? Science, 260 (5115) (1993), pp. 1773-1777

3 L. Thelander, P. ReichardReduction of ribonucleotides Annu Rev Biochem, 48 (1979), pp. 133-158

4 M. Fontecave, P. Nordlund, H. Eklund, et al.The redox centers of ribonucleotide reductase of Escherichia coli Adv Enzymol Relat Areas Mol Biol, 65 (1992), pp. 147-183

5 R.L. Blakley, H.A. BarkerCobamide stimulation of the reduction of ribotides to deoxyribotides in Lactobacillus leichmannii Biochem Biophys Res Commun, 16 (5) (1964), pp. 391-397

6 R. Eliasson, M. Fontecave, H. Jörnvall, et al.The anaerobic ribonucleoside triphosphate reductase from Escherichia coli requires S-adenosylmethionine as a cofactor Proc Natl Acad Sci U S A, 87 (9) (1990), pp. 3314-3318

7 A. Willing, H. Follmann, G. AulingRibonucleotide reductase of Brevibacterium ammoniagenes is a manganese enzyme Eur J Biochem, 170 (3) (1988), pp. 603-611

8 B. Zhou, Y. YenCharacterization of the human ribonucleotide reductase M2 subunit gene; genomic structure and promoter analyses Cytogenet Cell Genet, 95 (1–2) (2001), pp. 52-59

9 J.B. Park, M. LevineCharacterization of the promoter of the human ribonucleotide reductase R2 gene Biochem Biophys Res Commun, 267 (2) (2000), pp. 651-657

10 A. Chabes, L. ThelanderControlled protein degradation regulates ribonucleotide reductase activity in proliferating mammalian cells during the normal cell cycle and in response to DNA damage and replication blocks J Biol Chem, 275 (23) (2000), pp. 17747-17753

11 N. Pavloff, D. Rivard, S. Masson, et al.Sequence analysis of the large and small subunits of human ribonucleotide reductase DNA Seq, 2 (4) (1992), pp. 227-234

12 M. Thelander, L. ThelanderMolecular cloning and expression of the functional gene encoding the M2 subunit of mouse ribonucleotide reductase: a new dominant marker gene EMBO J, 8 (9) (1989), pp. 2475-2479

13 H. Eklund, U. Uhlin, M. Färnegårdh, et al.Structure and function of the radical enzyme ribonucleotide reductase Prog Biophys Mol Biol, 77 (3) (2001), pp. 177-268

14 M. Kolberg, K.R. Strand, P. Graff, et al.Structure, function, and mechanism of ribonucleotide reductases Biochim Biophys Acta, 1699 (1–2) (2004), pp. 1-34

15 B. Zhou, L. Su, Y.C. Yuan, et al.Structural basis on the dityrosyl-diiron radical cluster and the functional differences of human ribonucleotide reductase small subunits hp53R2 and hRRM2 Mol Cancer Ther, 9 (6) (2010), pp. 1669-1679

16 B. Zhou, X. Mo, X. Liu, et al.Human ribonucleotide reductase M2 subunit gene amplification and transcriptional regulation in a homogeneous staining chromosome region responsible for the mechanism of drug resistance Cytogenet Cell Genet, 95 (1–2) (2001), pp. 34-42

17 S. Eriksson, A. Gräslund, S. Skog, et al.Cell cycle-dependent regulation of mammalian ribonucleotide reductase. The S phase-correlated increase in subunit M2 is regulated by de novo protein synthesis J Biol Chem, 259 (19) (1984), pp. 11695-11700

18 A.L. Chabes, S. Björklund, L.S. ThelanderPhase-specific transcription of the mouse ribonucleotide reductase R2 gene requires both a proximal repressive E2F-binding site and an upstream promoter activating region J Biol Chem, 279 (11) (2004), pp. 10796-10807

19 X. Qian, D. Strahs, T. SchlickDynamic simulations of 13 TATA variants refine kinetic hypotheses of sequence/activity relationships J Mol Biol, 308 (4) (2001), pp. 681-703

20 I. Kotova, A.L. Chabes, S. Lobov, et al.Sequences downstream of the transcription initiation site are important for proper initiation and regulation of mouse ribonucleotide reductase R2 gene transcription Eur J Biochem, 270 (8) (2003), pp. 1791-1801

21 T. Bhuiyan, H.T.M. TimmersPromoter recognition: putting TFIID on the spot Trends Cell Biol, 29 (9) (2019), pp. 752-763

22 B. Wasylyk, R. Derbyshire, A. Guy, et al.Specific in vitro transcription of conalbumin gene is drastically decreased by single-point mutation in T-A-T-a box homology sequence Proc Natl Acad Sci U S A, 77 (12) (1980), pp. 7024-7028

23 L. Vo Ngoc, Y.L. Wang, G.A. Kassavetis, et al.The punctilious RNA polymerase II core promoter Genes Dev, 31 (13) (2017), pp. 1289-1301

24 B. Pasculli, R. Barbano, P. ParrellaEpigenetics of breast cancer: biology and clinical implication in the era of precision medicine Semin Cancer Biol, 51 (2018), pp. 22-35

25 J. Jovanovic, J.A. Rønneberg, J. Tost, et al.The epigenetics of breast cancer Mol Oncol, 4 (3) (2010), pp. 242-254

26 L. Qi, B. Zhou, J. Chen, et al.Significant prognostic values of differentially expressed-aberrantly methylated hub genes in breast cancer J Cancer, 10 (26) (2019), pp. 6618-6634

27 K. Luger, A.W. Mäder, R.K. Richmond, et al.Crystal structure of the nucleosome core particle at 2.8 A resolution Nature, 389 (6648) (1997), pp. 251-260

28 B.D. Strahl, C.D. AllisThe language of covalent histone modifications Nature, 403 (6765) (2000), pp. 41-45

29 J. Li, J.H. Ahn, G.G. WangUnderstanding histone H3 lysine 36 methylation and its deregulation in disease Cell Mol Life Sci, 76 (15) (2019), pp. 2899-2916

30 T. Zhang, S. Cooper, N. BrockdorffThe interplay of histone modifications - writers that read EMBO Rep, 16 (11) (2015), pp. 1467-1481

31 C. Xiao, T. Fan, H. Tian, et al.H3K36 trimethylation-mediated biological functions in cancer Clin Epigenetics, 13 (2021), p. 199

32 U.T.F. Lam, E.S. ChenMolecular mechanisms in governing genomic stability and tumor suppression by the SETD2 H3K36 methyltransferase Int J Biochem Cell Biol, 144 (2022), Article 106155

33 S.X. Pfister, E. Markkanen, Y. Jiang, et al.Inhibiting WEE1 selectively kills histone H3K36me3-deficient cancers by dNTP starvation Cancer Cell, 28 (5) (2015), pp. 557-568

34 M. Vermeulen, H.C. Eberl, F. Matarese, et al.Quantitative interaction proteomics and genome-wide profiling of epigenetic histone marks and their readers Cell, 142 (6) (2010), pp. 967-980

35 R.C. BaxterIGF binding proteins in cancer: mechanistic and clinical insights Nat Rev Cancer, 14 (5) (2014), pp. 329-341

36 F. Hakuno, S.I. TakahashiIGF1 receptor signaling pathways J Mol Endocrinol, 61 (1) (2018), pp. T69-T86

37 S. Zhuang, L. Li, Y. Zang, et al.RRM2 elicits the metastatic potential of breast cancer cells by regulating cell invasion, migration and VEGF expression via the PI3K/AKT signaling Oncol Lett, 19 (4) (2020), pp. 3349-3355

38 L. Cui, L. Yan, X. Guan, et al.Anti-tumor effect of apatinib and relevant mechanisms in liposarcoma Front Oncol, 11 (2021), Article 739139

39 S. Li, H. Mai, Y. Zhu, et al.MicroRNA-4500 inhibits migration, invasion, and angiogenesis of breast cancer cells via RRM2-dependent MAPK signaling pathway Mol Ther Nucleic Acids, 21 (2020), pp. 278-289

40 G. Rieunier, X. Wu, L.E. Harris, et al.Targeting IGF perturbs global replication through ribonucleotide reductase dysfunction Cancer Res, 81 (8) (2021), pp. 2128-2141

41 H. Lee, W.J. Kim, H.G. Kang, et al.Upregulation of LAMB1 via ERK/c-Jun axis promotes gastric cancer growth and motility Int J Mol Sci, 22 (2) (2021), p. 626

42 T. Aleksic, N. Gray, X. Wu, et al.Nuclear IGF1R interacts with regulatory regions of chromatin to promote RNA polymerase II recruitment and gene expression associated with advanced tumor stage Cancer Res, 78 (13) (2018), pp. 3497-3509

43 Z. Fu, S. Zhang, B. Wang, et al.Annexin A1: a double-edged sword as novel cancer biomarker Clin Chim Acta, 504 (2020), pp. 36-42

44 T.G. Araújo, S.T.S. Mota, H.S.V. Ferreira, et al.Annexin A1 as a regulator of immune response in cancer Cells, 10 (9) (2021), p. 2245

45 W. Xiong, B. Zhang, H. Yu, et al.RRM2 regulates sensitivity to sunitinib and PD-1 blockade in renal cancer by stabilizing ANXA1 and activating the AKT pathway Adv Sci (Weinh), 8 (18) (2021), Article e2100881

46 Z. Boudhraa, C. Merle, D. Mazzocut, et al.Characterization of pro-invasive mechanisms and N-terminal cleavage of ANXA1 in melanoma Arch Dermatol Res, 306 (10) (2014), pp. 903-914

47 Y. Li, D. YeMolecular biology for formyl peptide receptors in human diseases J Mol Med, 91 (7) (2013), pp. 781-789

48 T. Khau, S.Y. Langenbach, M. Schuliga, et al.Annexin-1 signals mitogen-stimulated breast tumor cell proliferation by activation of the formyl peptide receptors (FPRs) 1 and 2 FASEB J, 25 (2) (2011), pp. 483-496

49 L. Wei, L. Li, L. Liu, et al.Knockdown of annexin-A1 inhibits growth, migration and invasion of glioma cells by suppressing the PI3K/Akt signaling pathway ASN Neuro, 13 (2021), Article 17590914211001218

50 C.M.V. Barbosa, R.A. Fock, A.A. Hastreiter, et al.Extracellular annexin-A1 promotes myeloid/granulocytic differentiation of hematopoietic stem/progenitor cells via the Ca2+/MAPK signalling transduction pathway Cell Death Discov, 5 (2019), p. 135

51 P. Bist, Q.H. Phua, S. Shu, et al.Annexin-A1 controls an ERK-RhoA-NFκB activation loop in breast cancer cells Biochem Biophys Res Commun, 461 (1) (2015), pp. 47-53

52 L.N. Kent, G. LeoneThe broken cycle: E2F dysfunction in cancer Nat Rev Cancer, 19 (6) (2019), pp. 326-338

53 J.N. Lavoie, G. L'Allemain, A. Brunet, et al.Cyclin D1 expression is regulated positively by the p42/p44MAPK and negatively by the p38/HOGMAPK pathway J Biol Chem, 271 (34) (1996), pp. 20608-20616

54 S.M. Rubin, J. Sage, J.M. SkotheimIntegrating old and new paradigms of G1/S control Mol Cell, 80 (2) (2020), pp. 183-192

55 G.J. Lindeman, S. Gaubatz, D.M. Livingston, et al.The subcellular localization of E2F-4 is cell-cycle dependent Proc Natl Acad Sci U S A, 94 (10) (1997), pp. 5095-5100

56 J. Magae, C.L. Wu, S. Illenye, et al.Nuclear localization of DP and E2F transcription factors by heterodimeric partners and retinoblastoma protein family members J Cell Sci, 109 (Pt 7) (1996), pp. 1717-1726

57 R. Verona, K. Moberg, S. Estes, et al.E2F activity is regulated by cell cycle-dependent changes in subcellular localization Mol Cell Biol, 17 (12) (1997), pp. 7268-7282

58 R. Wang, X. Li, C. Sun, et al.The ATPase Pontin is a key cell cycle regulator by amplifying E2F1 transcription response in glioma Cell Death Dis, 12 (2) (2021), p. 141

59 N.B. La ThangueThe Yin and Yang of E2F-1: balancing life and death Nat Cell Biol, 5 (7) (2003), pp. 587-589

60 E.C. Cho, S. Zheng, S. Munro, et al.Arginine methylation controls growth regulation by E2F-1 EMBO J, 31 (7) (2012), pp. 1785-1797

61 S. Zheng, J. Moehlenbrink, Y.C. Lu, et al.Arginine methylation-dependent reader-writer interplay governs growth control by E2F-1 Mol Cell, 52 (1) (2013), pp. 37-51

62 V. Cura, J. CavarelliStructure, activity and function of the PRMT2 protein arginine methyltransferase Life (Basel), 11 (11) (2021), p. 1263

63 F. Bai, H.L. Chan, A. Scott, et al.BRCA1 suppresses epithelial-to-mesenchymal transition and stem cell dedifferentiation during mammary and tumor development Cancer Res, 74 (21) (2014), pp. 6161-6172

64 F. Bai, C. Wang, X. Liu, et al.Loss of function of BRCA1 promotes EMT in mammary tumors through activation of TGFβR2 signaling pathway Cell Death Dis, 13 (3) (2022), p. 195

65 R.D. Rasmussen, M.K. Gajjar, L. Tuckova, et al.BRCA1-regulated RRM2 expression protects glioblastoma cells from endogenous replication stress and promotes tumorigenicity Nat Commun, 7 (2016), Article 13398

66 J. Musa, M.M. Aynaud, O. Mirabeau, et al.MYBL2 (B-Myb):a central regulator of cell proliferation, cell survival and differentiation involved in tumorigenesis Cell Death Dis, 8 (6) (2017), Article e2895

67 R. Bayley, C. Ward, P. GarciaMYBL2 amplification in breast cancer: molecular mechanisms and therapeutic potential Biochim Biophys Acta Rev Cancer, 1874 (2) (2020), Article 188407

68 Q. Liu, L. Guo, H. Qi, et al.A MYBL2 complex for RRM2 transactivation and the synthetic effect of MYBL2 knockdown with WEE1 inhibition against colorectal cancer Cell Death Dis, 12 (7) (2021), p. 683

69 Z. Xing, A. Lin, C. Li, et al.lncRNA directs cooperative epigenetic regulation downstream of chemokine signals Cell, 159 (5) (2014), pp. 1110-1125

70 A. Kandettu, R. Radhakrishnan, S. Chakrabarty, et al.The emerging role of miRNA clusters in breast cancer progression Biochim Biophys Acta Rev Cancer, 1874 (2) (2020), Article 188413

71 W.H. Liang, N. Li, Z.Q. Yuan, et al.DSCAM-AS1 promotes tumor growth of breast cancer by reducing miR-204-5p and up-regulating RRM2 Mol Carcinog, 58 (4) (2019), pp. 461-473

72 S.M. DuThe SNHG16/miR-30a axis promotes breast cancer cell proliferation and invasion by regulating RRM2 Neoplasma, 67 (3) (2020), pp. 567-575

73 H. Feng, Q. Wang, W. Xiao, et al.LncRNA TTN-AS1 regulates miR-524-5p and RRM2 to promote breast cancer progression Onco Targets Ther, 13 (2020), pp. 4799-4811

74 J. Tait-Mulder, K. Hodge, D. Sumpton, et al.The conversion of formate into purines stimulates mTORC1 leading to CAD-dependent activation of pyrimidine synthesis Cancer Metab, 8 (2020), p. 20

75 X. Fu, P. Li, L. Zhang, et al.Activation of Rictor/mTORC2 signaling acts as a pivotal strategy to protect against sensorineural hearing loss Proc Natl Acad Sci U S A, 119 (10) (2022), Article e2107357119

76 R. Shams, Y. Ito, H. MiyatakeMapping of mTOR drug targets: featured platforms for anti-cancer drug discovery Pharmacol Ther, 232 (2022), Article 108012

77 Y. Yin, J. Long, Y. Sun, et al.The function and clinical significance of eIF3 in cancer Gene, 673 (2018), pp. 130-133

78 Q. Chen, B. Yang, N. Nass, et al.Impact of eukaryotic translation initiation factors on breast cancer: still much to investigate Cancers, 12 (7) (2020), p. 1984

79 S. Ma, Z. Dong, Y. Huang, et al.eIF3a regulation of mTOR signaling and translational control via HuR in cellular response to DNA damage Oncogene, 41 (17) (2022), pp. 2431-2443

80 X. Qin, B. Jiang, Y. Zhang4E-BP1, a multifactor regulated multifunctional protein Cell Cycle, 15 (6) (2016), pp. 781-786

81 Z. He, X. Hu, W. Liu, et al.P53 suppresses ribonucleotide reductase via inhibiting mTORC1 Oncotarget, 8 (25) (2017), pp. 41422-41431

82 K.L. Goss, S.L. Koppenhafer, T. Waters, et al.The translational repressor 4E-BP1 regulates RRM2 levels and functions as a tumor suppressor in Ewing sarcoma tumors Oncogene, 40 (3) (2021), pp. 564-577

83 L. Hauffe, D. Picard, J. Musa, et al.Eukaryotic translation initiation factor 4E binding protein 1 (EIF4EBP1) expression in glioblastoma is driven by ETS1- and MYBL2-dependent transcriptional activation Cell Death Discov, 8 (1) (2022), p. 91

84 S. Zhang, L. Yan, C. Cui, et al.Downregulation of RRM2 attenuates retroperitoneal liposarcoma progression via the Akt/mTOR/4EBP1 pathway: clinical, biological, and therapeutic significance Onco Targets Ther, 13 (2020), pp. 6523-6537

85 Z. Dong, L.H. Liu, B. Han, et al.Role of eIF3 p170 in controlling synthesis of ribonucleotide reductase M2 and cell growth Oncogene, 23 (21) (2004), pp. 3790-3801

86 S. Sridharan, A. BasuDistinct roles of mTOR targets S6K1 and S6K2 in breast cancer Int J Mol Sci, 21 (4) (2020), p. 1199

87 L.A. Julien, A. Carriere, J. Moreau, et al.mTORC1-activated S6K1 phosphorylates rictor on threonine 1135 and regulates mTORC2 signaling Mol Cell Biol, 30 (4) (2010), pp. 908-921

88 M.W. Greene, H. Sakaue, L. Wang, et al.Modulation of insulin-stimulated degradation of human insulin receptor substrate-1 by serine 312 phosphorylation J Biol Chem, 278 (10) (2003), pp. 8199-8211

89 B. Denhez, M. Rousseau, C. Spino, et al.Saturated fatty acids induce insulin resistance in podocytes through inhibition of IRS1 via activation of both IKKβ and mTORC1 Sci Rep, 10 (2020), Article 21628

90 Q. Zhang, X. Zhou, M. Wan, et al.FoxP3-miR-150-5p/3p suppresses ovarian tumorigenesis via an IGF1R/IRS1 pathway feedback loop Cell Death Dis, 12 (3) (2021), p. 275

91 L.M. Williams, A.Y. RudenskyMaintenance of the Foxp3-dependent developmental program in mature regulatory T cells requires continued expression of Foxp3 Nat Immunol, 8 (3) (2007), pp. 277-284

92 V. Hashemi, L.A. Maleki, M. Esmaily, et al.Regulatory T cells in breast cancer as a potent anti-cancer therapeutic target Int Immunopharmacol, 78 (2020), Article 106087

93 S. Haxhinasto, D. Mathis, C. BenoistThe AKT-mTOR axis regulates de novo differentiation of CD4+Foxp3+ cells J Exp Med, 205 (3) (2008), pp. 565-574

94 W. Li, F. Li, X. Zhang, et al.Insights into the post-translational modification and its emerging role in shaping the tumor microenvironment Signal Transduct Target Ther, 6 (2021), p. 422

95 M. Shvedunova, A. AkhtarModulation of cellular processes by histone and non-histone protein acetylation Nat Rev Mol Cell Biol, 23 (5) (2022), pp. 329-349

96 D.M. Newman, A.K. Voss, T. Thomas, et al.Essential role for the histone acetyltransferase KAT7 in T cell development, fitness, and survival J Leukoc Biol, 101 (4) (2017), pp. 887-892

97 Y. Zhang, X. Long, X. Ruan, et al.SIRT2-mediated deacetylation and deubiquitination of C/EBPβ prevents ethanol-induced liver injury Cell Discov, 7 (2021), p. 93

98 G. Chen, Y. Luo, K. Warncke, et al.Acetylation regulates ribonucleotide reductase activity and cancer cell growth Nat Commun, 10 (2019), p. 3213

99 J.C. Saldivar, D. Cortez, K.A. CimprichThe essential kinase ATR: ensuring faithful duplication of a challenging genome Nat Rev Mol Cell Biol, 18 (10) (2017), pp. 622-636

100 S.T. Kim, D.S. Lim, C.E. Canman, et al.Substrate specificities and identification of putative substrates of ATM kinase family members J Biol Chem, 274 (53) (1999), pp. 37538-37543

101 F. Dang, L. Nie, W. WeiUbiquitin signaling in cell cycle control and tumorigenesis Cell Death Differ, 28 (2) (2021), pp. 427-438

102 P.C.A. da Fonseca, E.H. Kong, Z. Zhang, et al.Structures of APC/C(Cdh1) with substrates identify Cdh1 and Apc10 as the D-box co-receptor Nature, 470 (7333) (2011), pp. 274-278

103 A.L. Chabes, C.M. Pfleger, M.W. Kirschner, et al.Mouse ribonucleotide reductase R2 protein: a new target for anaphase-promoting complex-Cdh1-mediated proteolysis Proc Natl Acad Sci U S A, 100 (7) (2003), pp. 3925-3929

104 Y.J. Kim, Y. Zhao, J.K. Myung, et al.Suppression of breast cancer progression by FBXL16 via oxygen-independent regulation of HIF1α stability Cell Rep, 37 (8) (2021), Article 109996

105 C. Bai, R. Richman, S.J. ElledgeHuman cyclin F EMBO J, 13 (24) (1994), pp. 6087-6098

106 V. D'Angiolella, V. Donato, F.M. Forrester, et al.Cyclin F-mediated degradation of ribonucleotide reductase M2 controls genome integrity and DNA repair Cell, 149 (5) (2012), pp. 1023-1034

107 S.C. Chang, C.S. Hung, B.X. Zhang, et al.A novel signature of CCNF-associated E3 ligases collaborate and counter each other in breast cancer Cancers, 13 (12) (2021), p. 2873

108 T. Cardozo, M. PaganoThe SCF ubiquitin ligase: insights into a molecular machine Nat Rev Mol Cell Biol, 5 (9) (2004), pp. 739-751

109 A.C. Carrano, E. Eytan, A. Hershko, et al.SKP2 is required for ubiquitin-mediated degradation of the CDK inhibitor p27 Nat Cell Biol, 1 (4) (1999), pp. 193-199

110 G. Bornstein, J. Bloom, D. Sitry-Shevah, et al.Role of the SCFSkp2 ubiquitin ligase in the degradation of p21Cip1 in S phase J Biol Chem, 278 (28) (2003), pp. 25752-25757

111 G.G. Xiao, B.S. Zhou, G. Somlo, et al.Identification of F-box/LLR-repeated protein 17 as potential useful biomarker for breast cancer therapy Cancer Genomics Proteomics, 5 (3–4) (2008), pp. 151-160

112 P. Nurse, P. ThuriauxRegulatory genes controlling mitosis in the fission yeast Schizosaccharomyces pombe Genetics, 96 (3) (1980), pp. 627-637

113 C.H. McGowan, P. RussellHuman Wee1 kinase inhibits cell division by phosphorylating p34cdc2 exclusively on Tyr15 EMBO J, 12 (1) (1993), pp. 75-85

114 C.R. Elbæk, V. Petrosius, C.S. SørensenWEE1 kinase limits CDK activities to safeguard DNA replication and mitotic entry Mutat Res, 819–820 (2020), Article 111694

115 S.L. Koppenhafer, K.L. Goss, W.W. Terry, et al.Inhibition of the ATR-CHK1 pathway in ewing sarcoma cells causes DNA damage and apoptosis via the CDK2-mediated degradation of RRM2 Mol Cancer Res, 18 (1) (2020), pp. 91-104

116 H. Gaillard, T. García-Muse, A. AguileraReplication stress and cancer Nat Rev Cancer, 15 (5) (2015), pp. 276-289

117 L. Wang, X. Zhao, J. Fu, et al.The role of tumour metabolism in cisplatin resistance Front Mol Biosci, 8 (2021), Article 691795

118 T. Kato, H. Ono, M. Fujii, et al.Cytoplasmic RRM1 activation as an acute response to gemcitabine treatment is involved in drug resistance of pancreatic cancer cells PLoS One, 16 (6) (2021), Article e0252917

119 Y. Yen, S.P. Grill, G.E. Dutschman, et al.Characterization of a hydroxyurea-resistant human KB cell line with supersensitivity to 6-thioguanine Cancer Res, 54 (14) (1994), pp. 3686-3691

120 B.S. Zhou, N.Y. Hsu, B.C. Pan, et al.Overexpression of ribonucleotide reductase in transfected human KB cells increases their resistance to hydroxyurea: M2 but not M1 is sufficient to increase resistance to hydroxyurea in transfected cells Cancer Res, 55 (6) (1995), pp. 1328-1333

121 B. Das, N. Jain, B. MallickpiR-39980 mediates doxorubicin resistance in fibrosarcoma by regulating drug accumulation and DNA repair Commun Biol, 4 (2021), p. 1312

122 Y. Zhao, Y. Zheng, Y. Zhu, et al.M1 macrophage-derived exosomes loaded with gemcitabine and deferasirox against chemoresistant pancreatic cancer Pharmaceutics, 13 (9) (2021), p. 1493

123 F. Un, C. Qi, M. Prosser, et al.Modulating ICBP90 to suppress human ribonucleotide reductase M2 induction restores sensitivity to hydroxyurea cytotoxicity Anticancer Res, 26 (4B) (2006), pp. 2761-2767

124 K.N. Shah, K.R. Mehta, D. Peterson, et al.AKT-induced tamoxifen resistance is overturned by RRM2 inhibition Mol Cancer Res, 12 (3) (2014), pp. 394-407

125 K.N. Shah, E.A. Wilson, R. Malla, et al.Targeting ribonucleotide reductase M2 and NF-κB activation with didox to circumvent tamoxifen resistance in breast cancer Mol Cancer Ther, 14 (11) (2015), pp. 2411-2421

126 Z.N. Li, Y. Shu, C.G. Chen, et al.Acquired tamoxifen resistance is surmounted by GW8510 through ribonucleotide reductase M2 downregulation-mediated autophagy induction Biochem Biophys Res Commun, 528 (3) (2020), pp. 554-560

127 S. Zhou, J. Li, H. Xu, et al.Liposomal curcumin alters chemosensitivity of breast cancer cells to Adriamycin via regulating microRNA expression Gene, 622 (2017), pp. 1-12

128 M. Muto, Y. Kanari, E. Kubo, et al.Targeted disruption of Np95 gene renders murine embryonic stem cells hypersensitive to DNA damaging agents and DNA replication blocks J Biol Chem, 277 (37) (2002), pp. 34549-34555

129 A. Nishiyama, L. Yamaguchi, J. Sharif, et al.Uhrf1-dependent H3K23 ubiquitylation couples maintenance DNA methylation and replication Nature, 502 (7470) (2013), pp. 249-253

130 R. Daylami, D.J. Muilenburg, S. Virudachalam, et al.Pegylated arginine deiminase synergistically increases the cytotoxicity of gemcitabine in human pancreatic cancer J Exp Clin Cancer Res, 33 (2014), p. 102

131 I. Kotova, A.L. Chabes, B. Segerman, et al.A mouse in vitro transcription system reconstituted from highly purified RNA polymerase II, TFIIH and recombinant TBP, TFIIB, TFIIE and TFIIF Eur J Biochem, 268 (16) (2001), pp. 4527-4536

132 X. Liu, B. Zhou, L. Xue, et al.Nuclear factor Y regulation and promoter transactivation of human ribonucleotide reductase subunit M2 gene in a Gemcitabine resistant KB clone Biochem Pharmacol, 67 (8) (2004), pp. 1499-1511

133 P. Chen, J.N. Wu, Y. Shu, et al.Gemcitabine resistance mediated by ribonucleotide reductase M2 in lung squamous cell carcinoma is reversed by GW8510 through autophagy induction Clin Sci (Lond), 132 (13) (2018), pp. 1417-1433

134 Y.G. Goan, B. Zhou, E. Hu, et al.Overexpression of ribonucleotide reductase as a mechanism of resistance to 2, 2-difluorodeoxycytidine in the human KB cancer cell line Cancer Res, 59 (17) (1999), pp. 4204-4207

135 S.J. Dixon, K.M. Lemberg, M.R. Lamprecht, et al.Ferroptosis: an iron-dependent form of nonapoptotic cell death Cell, 149 (5) (2012), pp. 1060-1072

136 B.R. Stockwell, J.P. Friedmann Angeli, H. Bayir, et al.Ferroptosis: a regulated cell death nexus linking metabolism, redox biology, and disease Cell, 171 (2) (2017), pp. 273-285

137 Y. Jiang, R. Tao, Z. Shen, et al.Enzymatic production of glutathione by bifunctional γ-glutamylcysteine synthetase/glutathione synthetase coupled with in vitro acetate kinase-based ATP generation Appl Biochem Biotechnol, 180 (7) (2016), pp. 1446-1455

138 A. Tarangelo, J. Rodencal, J.T. Kim, et al.Nucleotide biosynthesis links glutathione metabolism to ferroptosis sensitivity Life Sci Alliance, 5 (4) (2022), Article e202101157

139 Z.B. Ke, Q. You, J.B. Sun, et al.A novel ferroptosis-based molecular signature associated with biochemical recurrence-free survival and tumor immune microenvironment of prostate cancer Front Cell Dev Biol, 9 (2021), Article 774625

140 X. Zhang, L. Du, Y. Qiao, et al.Ferroptosis is governed by differential regulation of transcription in liver cancer Redox Biol, 24 (2019), Article 101211

141 B. Tang, W. Xu, Y. Wang, et al.Identification of critical ferroptosis regulators in lung adenocarcinoma that RRM2 facilitates tumor immune infiltration by inhibiting ferroptotic death Clin Immunol, 232 (2021), Article 108872

142 W. Chen, L. Zhang, K. Zhang, et al.Reciprocal regulation of autophagy and dNTP pools in human cancer cells Autophagy, 10 (7) (2014), pp. 1272-1284

143 L.B. Kennedy, A.K.S. SalamaA review of cancer immunotherapy toxicity CA Cancer J Clin, 70 (2) (2020), pp. 86-104

144 J. Nam, S. Son, K.S. Park, et al.Cancer nanomedicine for combination cancer immunotherapy Nat Rev Mater, 4 (6) (2019), pp. 398-414

145 Y.Z. Mazzu, J. Armenia, S. Nandakumar, et al.Ribonucleotide reductase small subunit M2 is a master driver of aggressive prostate cancer Mol Oncol, 14 (8) (2020), pp. 1881-1897

146 G. Roviello, L.F. Iannone, M. Bersanelli, et al.The gut microbiome and efficacy of cancer immunotherapy Pharmacol Ther, 231 (2022), Article 107973

147 A.H. Sharpe, E.J. Wherry, R. Ahmed, et al.The function of programmed cell death 1 and its ligands in regulating autoimmunity and infection Nat Immunol, 8 (3) (2007), pp. 239-245

148 Y. Iwai, J. Hamanishi, K. Chamoto, et al.Cancer immunotherapies targeting the PD-1 signaling pathway J Biomed Sci, 24 (2017), p. 26

149 T. Okazaki, T. HonjoThe PD-1-PD-L pathway in immunological tolerance Trends Immunol, 27 (4) (2006), pp. 195-201

150 H. Dong, S.E. Strome, D.R. Salomao, et al.Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion Nat Med, 8 (8) (2002), pp. 793-800

151 W. Zou, J.D. Wolchok, L. ChenPD-L1 (B7-H1) and PD-1 pathway blockade for cancer therapy: mechanisms, response biomarkers, and combinations Sci Transl Med, 8 (328) (2016), p. 328rv4

152 B.T. Fife, K.E. Pauken, T.N. Eagar, et al.Interactions between PD-1 and PD-L1 promote tolerance by blocking the TCR-induced stop signal Nat Immunol, 10 (11) (2009), pp. 1185-1192

153 J. Zhang, W. Fang, T. Qin, et al.Co-expression of PD-1 and PD-L1 predicts poor outcome in nasopharyngeal carcinoma Med Oncol, 32 (3) (2015), p. 86

154 D. Ren, Y. Hua, B. Yu, et al.Predictive biomarkers and mechanisms underlying resistance to PD1/PD-L1 blockade cancer immunotherapy Mol Cancer, 19 (2020), p. 19

155 A. Palazon, A.W. Goldrath, V. Nizet, et al.HIF transcription factors, inflammation, and immunity Immunity, 41 (4) (2014), pp. 518-528

156 F. Luo, F.T. Lu, J.X. Cao, et al.HIF-1α inhibition promotes the efficacy of immune checkpoint blockade in the treatment of non-small cell lung cancer Cancer Lett, 531 (2022), pp. 39-56

157 C.M. Bailey, Y. Liu, M. Liu, et al.Targeting HIF-1α abrogates PD-L1-mediated immune evasion in tumor microenvironment but promotes tolerance in normal tissues J Clin Invest, 132 (9) (2022), Article e150846

158 T.A. Wynn, K.M. VannellaMacrophages in tissue repair, regeneration, and fibrosis Immunity, 44 (3) (2016), pp. 450-462

159 A. Mantovani, F. Marchesi, A. Malesci, et al.Tumour-associated macrophages as treatment targets in oncology Nat Rev Clin Oncol, 14 (7) (2017), pp. 399-416

160 M.L. Kuo, H.S. Hwang, P.R. Sosnay, et al.Overexpression of the R2 subunit of ribonucleotide reductase in human nasopharyngeal cancer cells reduces radiosensitivity Cancer J, 9 (4) (2003), pp. 277-285

161 M. Griesshammer, K. Wille, P. Sadjadian, et al.A review of hydroxyurea-related cutaneous adverse events Expert Opin Drug Saf, 20 (12) (2021), pp. 1515-1521

162 S. Nyholm, L. Thelander, A. GräslundReduction and loss of the iron center in the reaction of the small subunit of mouse ribonucleotide reductase with hydroxyurea Biochemistry, 32 (43) (1993), pp. 11569-11574

163 M. Asperti, L. Cantamessa, S. Ghidinelli, et al.The antitumor didox acts as an iron Chelator in hepatocellular carcinoma cells Pharmaceuticals (Basel), 12 (3) (2019), p. 129

164 H.L. Elford, G.L. Wampler, B. van't RietNew ribonucleotide reductase inhibitors with antineoplastic activity Cancer Res, 39 (3) (1979), pp. 844-851

165 Z. Horvath, W. Bauer, T. Hoechtl, et al.Combination chemotherapy of BCNU and Didox acts synergystically in 9L glioma cells Nucleosides Nucleotides Nucleic Acids, 23 (8–9) (2004), pp. 1531-1535

166 S.A. Khaleel, A.M. Al-Abd, A.A. Ali, et al.Didox and resveratrol sensitize colorectal cancer cells to doxorubicin via activating apoptosis and ameliorating P-glycoprotein activity Sci Rep, 6 (2016), Article 36855

167 Y. Shang, X. Li, Z. Li, et al.Theoretical study on the radical scavenging activity and mechanism of four kinds of Gnetin molecule Food Chem, 378 (2022), Article 131975

168 Q. Sun, Z. Ye, Y. Qin, et al.Oncogenic function of TRIM2 in pancreatic cancer by activating ROS-related NRF2/ITGB7/FAK axis Oncogene, 39 (42) (2020), pp. 6572-6588

169 T. Cheng, C. Wang, Q. Lu, et al.Metformin inhibits the tumor-promoting effect of low-dose resveratrol, and enhances the anti-tumor activity of high-dose resveratrol by increasing its reducibility in triple negative breast cancer Free Radic Biol Med, 180 (2022), pp. 108-120

170 M. Fontecave, M. Lepoivre, E. Elleingand, et al.Resveratrol, a remarkable inhibitor of ribonucleotide reductase FEBS Lett, 421 (3) (1998), pp. 277-279

171 J.H. Lundberg, C.R. ChitambarInteraction of gallium nitrate with fludarabine and iron chelators: effects on the proliferation of human leukemic HL60 cells Cancer Res, 50 (20) (1990), pp. 6466-6470

172 G. Nocentini, F. Federici, R. Armellini, et al.Isolation of two cellular lines resistant to ribonucleotide reductase inhibitors to investigate the inhibitory activity of 2, 2'-bipyridyl-6-carbothioamide Anticancer Drugs, 1 (2) (1990), pp. 171-177

173 C.R. Chitambar, W.G. Matthaeus, W.E. Antholine, et al.Inhibition of leukemic HL60 cell growth by transferrin-Gallium: effects on ribonucleotide reductase and demonstration of drug synergy with hydroxyurea Blood, 72 (6) (1988), pp. 1930-1936

174 J. Li, L.M. Zheng, I. King, et al.Syntheses and antitumor activities of potent inhibitors of ribonucleotide reductase: 3-amino-4-methylpyridine-2-carboxaldehyde-thiosemicarba-zone (3-AMP), 3-amino-pyridine-2-carboxaldehyde-thiosemicarbazone (3-AP) and its water-soluble prodrugs Curr Med Chem, 8 (2) (2001), pp. 121-133

175 Y. Aye, M.J.C. Long, J. StubbeMechanistic studies of semicarbazone triapine targeting human ribonucleotide reductase in vitro and in mammalian cells: tyrosyl radical quenching not involving reactive oxygen species J Biol Chem, 287 (42) (2012), pp. 35768-35778

176 C.M. Nutting, C.M.L. van Herpen, A.B. Miah, et al.Phase II study of 3-AP Triapine in patients with recurrent or metastatic head and neck squamous cell carcinoma Ann Oncol, 20 (7) (2009), pp. 1275-1279

177 A.M. Traynor, J.W. Lee, G.K. Bayer, et al.A phase II trial of Triapine® (NSC# 663249) and gemcitabine as second line treatment of advanced non-small cell lung cancer: eastern Cooperative Oncology Group Study 1503 Invest New Drugs, 28 (1) (2010), pp. 91-97

178 C. Stefani, P.J. Jansson, E. Gutierrez, et al.Alkyl substituted 2'-benzoylpyridine thiosemicarbazone chelators with potent and selective anti-neoplastic activity: novel ligands that limit methemoglobin formation J Med Chem, 56 (1) (2013), pp. 357-370

179 S. Plamthottam, D. Sun, J. Van Valkenburgh, et al.Activity and electrochemical properties: iron complexes of the anticancer drug triapine and its analogs J Biol Inorg Chem, 24 (5) (2019), pp. 621-632

180 A.M. Senderowicz, E.A. SausvillePreclinical and clinical development of cyclin-dependent kinase modulators J Natl Cancer Inst, 92 (5) (2000), pp. 376-387

181 J.F. Zeidner, J.E. KarpClinical activity of alvocidib (flavopiridol) in acute myeloid leukemia Leuk Res, 39 (12) (2015), pp. 1312-1318

182 P.H. WiernikAlvocidib (flavopiridol) for the treatment of chronic lymphocytic leukemia Expert Opin Investig Drugs, 25 (6) (2016), pp. 729-734

183 M.B. Wilson, S.J. Schreiner, H.J. Choi, et al.Selective pyrrolo-pyrimidine inhibitors reveal a necessary role for Src family kinases in Bcr-Abl signal transduction and oncogenesis Oncogene, 21 (53) (2002), pp. 8075-8088

184 C.P. Jung, M.V. Motwani, G.K. SchwartzFlavopiridol increases sensitization to gemcitabine in human gastrointestinal cancer cell lines and correlates with down-regulation of ribonucleotide reductase M2 subunit Clin Cancer Res, 7 (8) (2001), pp. 2527-2536

185 M.S. Duxbury, H. Ito, M.J. Zinner, et al.Inhibition of SRC tyrosine kinase impairs inherent and acquired gemcitabine resistance in human pancreatic adenocarcinoma cells Clin Cancer Res, 10 (7) (2004), pp. 2307-2318

186 C.L. Chen, S.C. Hsu, D.K. Ann, et al.Arginine signaling and cancer metabolism Cancers, 13 (14) (2021), p. 3541

187 A. Matos, M. Carvalho, M. Bicho, et al.Arginine and arginases modulate metabolism, tumor microenvironment and prostate cancer progression Nutrients, 13 (12) (2021), p. 4503

188 C. Riess, F. Shokraie, C.F. Classen, et al.Arginine-depleting enzymes - an increasingly recognized treatment strategy for therapy-refractory malignancies Cell Physiol Biochem, 51 (2) (2018), pp. 854-870

189 S. Yao, F. Janku, K. Koenig, et al.Phase 1 trial of ADI-PEG 20 and liposomal doxorubicin in patients with metastatic solid tumors Cancer Med, 11 (2) (2022), pp. 340-347

190 B.C. Prudner, R. Rathore, A.M. Robinson, et al.Arginine starvation and docetaxel induce c-Myc-driven hENT1 surface expression to overcome gemcitabine resistance in ASS1-negative tumors Clin Cancer Res, 25 (16) (2019), pp. 5122-5134

191 M.B. Mannargudi, S. DebClinical pharmacology and clinical trials of ribonucleotide reductase inhibitors: is it a viable cancer therapy? J Cancer Res Clin Oncol, 143 (8) (2017), pp. 1499-1529

192 M.S. Duxbury, H. Ito, E. Benoit, et al.Retrovirally mediated RNA interference targeting the M2 subunit of ribonucleotide reductase: a novel therapeutic strategy in pancreatic cancer Surgery, 136 (2) (2004), pp. 261-269

193 M. MarzecSize does matter: piRNA and miRNA targeting Trends Biochem Sci, 47 (4) (2022), pp. 287-288

194 B. Das, J. Roy, N. Jain, et al.Tumor suppressive activity of PIWI-interacting RNA in human fibrosarcoma mediated through repression of RRM2 Mol Carcinog, 58 (3) (2019), pp. 344-357

195 T. Comont, M. Heiblig, E. Rivière, et al.Azacitidine for patients with Vacuoles, E1 Enzyme, X-linked, Autoinflammatory, Somatic syndrome (VEXAS) and myelodysplastic syndrome: data from the French VEXAS registry Br J Haematol, 196 (4) (2022), pp. 969-974

196 Z. Li, J. Zhang, M. Zhou, et al.Epigenetic therapy with chidamide alone or combined with 5-azacitidine exerts antitumour effects on acute myeloid leukaemia cells in vitro Oncol Rep, 47 (4) (2022), p. 66

197 J. Aimiuwu, H. Wang, P. Chen, et al.RNA-dependent inhibition of ribonucleotide reductase is a major pathway for 5-azacytidine activity in acute myeloid leukemia Blood, 119 (22) (2012), pp. 5229-5238

198 Y.Y. Hsieh, C.J. Chou, H.L. Lo, et al.Repositioning of a cyclin-dependent kinase inhibitor GW8510 as a ribonucleotide reductase M2 inhibitor to treat human colorectal cancer Cell Death Discov, 2 (2016), Article 16027

199 S.M. Wilhelm, C. Carter, L. Tang, et al.BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis Cancer Res, 64 (19) (2004), pp. 7099-7109

200 G. Pasqualetti, S. Ricciardi, V. Mey, et al.Synergistic cytotoxicity, inhibition of signal transduction pathways and pharmacogenetics of sorafenib and gemcitabine in human NSCLC cell lines Lung Cancer, 74 (2) (2011), pp. 197-205

201 P.M. Yang, L.S. Lin, T.P. LiuSorafenib inhibits ribonucleotide reductase regulatory subunit M2 (RRM2) in hepatocellular carcinoma cells Biomolecules, 10 (1) (2020), p. 117

202 C.W. Chen, Y. Li, S. Hu, et al.DHS (trans-4, 4'-dihydroxystilbene) suppresses DNA replication and tumor growth by inhibiting RRM2 (ribonucleotide reductase regulatory subunit M2) Oncogene, 38 (13) (2019), pp. 2364-2379

203 B. Zhou, L. Su, S. Hu, et al.A small-molecule blocking ribonucleotide reductase holoenzyme formation inhibits cancer cell growth and overcomes drug resistance Cancer Res, 73 (21) (2013), pp. 6484-6493

204 Y.Z. Mazzu, J. Armenia, G. Chakraborty, et al.A novel mechanism driving poor-prognosis prostate cancer: overexpression of the DNA repair gene, ribonucleotide reductase small subunit M2 (RRM2) Clin Cancer Res, 25 (14) (2019), pp. 4480-4492

205 H. Zhang, X. Liu, C.D. Warden, et al.Prognostic and therapeutic significance of ribonucleotide reductase small subunit M2 in estrogen-negative breast cancers BMC Cancer, 14 (2014), p. 664

206 X. Liu, Z. Xu, C. Hou, et al.Inhibition of hepatitis B virus replication by targeting ribonucleotide reductase M2 protein Biochem Pharmacol, 103 (2016), pp. 118-128

207 Q. Tang, L. Wu, M. Xu, et al.Osalmid, a novel identified RRM2 inhibitor, enhances radiosensitivity of esophageal cancer Int J Radiat Oncol, 108 (5) (2020), pp. 1368-1379

208 Z. Wu, Y. Zhan, L. Wang, et al.Identification of osalmid metabolic profile and active metabolites with anti-tumor activity in human hepatocellular carcinoma cells Biomed Pharmacother, 130 (2020), Article 110556

209 Y. Wang, F. Liang, Y. Zhou, et al.Sharp downregulation of hub genes associated with the pathogenesis of breast cancer from ductal carcinoma in situ to invasive ductal carcinoma Front Oncol, 11 (2021), Article 634569

210 C. Kretschmer, A. Sterner-Kock, F. Siedentopf, et al.Identification of early molecular markers for breast cancer Mol Cancer, 10 (2011), p. 15

211 P.F. Lainetti, A.F. Leis-Filho, R. Laufer-Amorim, et al.Mechanisms of resistance to chemotherapy in breast cancer and possible targets in drug delivery systems Pharmaceutics, 12 (12) (2020), p. 1193

212 D.G. Rüstem, S. Atay, H.H. Aydin, et al.Synergistic interactions between GW8510 and gemcitabine in an in vitro model of pancreatic cancer Anticancer Agents Med Chem, 21 (16) (2021), pp. 2204-2215

213 M.L. Kuo, T.J. KinsellaExpression of ribonucleotide reductase after ionizing radiation in human cervical carcinoma cells Cancer Res, 58 (10) (1998), pp. 2245-2252

214 B. Zhou, X. Liu, X. Mo, et al.The human ribonucleotide reductase subunit hRRM2 complements p53R2 in response to UV-induced DNA repair in cells with mutant p53 Cancer Res, 63 (20) (2003), pp. 6583-6594

215 E.Y. Ko, A. MoonNatural products for chemoprevention of breast cancer J Cancer Prev, 20 (4) (2015), pp. 223-231

216 M. Winkle, S.M. El-Daly, M. Fabbri, et al.Noncoding RNA therapeutics - challenges and potential solutions Nat Rev Drug Discov, 20 (8) (2021), pp. 629-651