Siegel RL, Miller KD, Sauer AG, et al., 2020, Colorectal Cancer Statistics, 2020. CA Cancer J Clin, 70145–64. DOI: 10.3322/caac.21601

Kaidanovich-Beilin O, Woodgett JR, 2011, GSK-3: Functional Insights From Cell Biology and Animal Models. Front Mol Neurosci. 4:40. DOI: 10.3389/fnmol.2011.00040

Mathers CD, Loncar D, 2006, Projections of Global Mortality and Burden of Disease from 2002 to 2030. PLoS Med, 3:e442. DOI: 10.1371/journal.pmed.0030442

Altchek A, 2003, Clues to Tumors: New Concepts of Symptoms, Signs, Syndromes, Paraneoplastic Syndromes, and Predisposition to Ovarian Cancer. In: Diagnosis and Management of Ovarian Disorders. Cambridge, Massachusetts: Academic Press. pp231–269. DOI: 10.1016/ B978-012053642-9/50024-7

Brenner H, Chen C, 2018, The Colorectal Cancer Epidemic: Challenges and Opportunities for Primary, Secondary and Tertiary Prevention. Br J Cancer, 119:785–92. DOI: 10.1038/s41416-018-0264-x

Yasui H, Tsurita G, Imai K, 2014, DNA Synthesis Inhibitors for the Treatment of Gastrointestinal Cancer. Expert Opin Pharmacother, 15:2361–72. DOI: 10.1517/14656566.2014.958074.

Papillon J, 2012, Rectal and Anal Cancers: Conservative Treatment by Irradiation an Alternative to Radical Surgery. Berlin: Springer Science and Business Media. DOI: 10.1007/978-3-642-68613-9

Jasperson KW, Patel SG, Ahnen DJ, 2017, APC-Associated Polyposis Conditions. GeneReviews®. Seattle, WA: University of Washington, Seattle.

Goldstein NS, Sanford W, Coffey M, et al., 1996, Lymph Node Recovery from Colorectal Resection Specimens Removed for Adenocarcinoma: Trends over Time and a Recommendation for a Minimum Number of Lymph Nodes to be Recovered. Am J Clin Pathol, 106:209–16. DOI: 10.1093/ajcp/106.2.209

Robinson TL, Sircar K, Hewlett BR, et al., 200, Gastrointestinal Stromal Tumors may Originate from a Subset of CD34-Positive Interstitial Cells of Cajal. Am J Pathol, 156:1157–63. DOI: 10.1016/S0002- 9440(10)64984-X.

Lee JK, Choi YL, Kwon M, et al., 2016, Mechanisms and Consequences of Cancer Genome Instability: Lessons From Genome Sequencing Studies. Annu Rev Pathol, 11:283– 312. DOI: 10.1146/annurev-pathol-012615-044446

Gollapudi P, 2019, Studies of Chromosome Damage Induced by Topoisomerase II Inhibitors in Human Cells (Doctoral Dissertation, UC Riverside).

Grady WM, Carethers JM, 2008, Genomic and Epigenetic Instability in Colorectal Cancer Pathogenesis. Gastroenterology, 135:1079–99. DOI: 10.1053/j. gastro.2008.07.076

Richardson B, Yung R, 1999, Role of DNA methylation in the regulation of cell function. J Lab Clin Med, 134:333–40. DOI: 10.1093/jn/132.8.2401S

Hawkins N, Norrie M, Cheong K, et al., 2002, CpG Island Methylation in Sporadic Colorectal Cancers and its Relationship to Microsatellite Instability. Gastroenterology, 122:1376–87. DOI: 10.1053/gast.2002.32997

Walsh MD, Clendenning M, Williamson E, et al., 2013, Expression of MUC2, MUC5AC, MUC5B, and MUC6 Mucins in Colorectal Cancers and their Association with the CpG Island Methylator Phenotype. Mod Pathol, 26:1642– 56. DOI: 10.1038/modpathol.2013.101

Papas TS, Kan NC, Watson DK, et al., 1985, Myc, a Genetic Element that is Shared by a Cellular Gene (proto-myc) and by Viruses with one (MC29) or Two (MH2) Onc Genes. InRNA Tumor Viruses, Oncogenes, Human Cancer and AIDS: On the Frontiers of Understanding. Springer, Boston, MA. pp1–13. DOI: 10.1007/978-1-4613-2583-3_1

Ilyas M, 2005, Wnt Signalling and the Mechanistic Basis of Tumour Development. J Pathol, 205:130–44. DOI: 10.1002/path.1692

Fodde R, Smits R, Clevers H, 2001, APC, Signal Transduction and Genetic Instability in Colorectal Cancer. Nat Rev Cancer, 1:55–67. DOI: 10.1038/35094067

Hientz K, Mohr A, Bhakta-Guha D, et al., 2017, The Role of p53 in Cancer Drug Resistance and Targeted Chemotherapy. Oncotarget, 8:8921. DOI: 10.18632/oncotarget.13475

Olumi AF, Grossfeld GD, Hayward SW, et al., 2000, Carcinoma-Associated Fibroblasts Stimulate Tumor Progression of Initiated Human Epithelium. Breast Cancer Res, 2:1. DOI: 10.1186/bcr138

Nasrallah A, El-Sibai M, 2014, Colorectal Cancer Causes and Treatments: A Minireview. Open Colorectal Cancer J, 7: 1–14. DOI: 10.2174/1876820201407010001

de Caestecker MP, Piek E, Roberts AB, 2000, Role of Transforming Growth Factor-β Signaling in Cancer. J Natl Cancer Inst, 92:1388–402. DOI: 10.1093/jnci/92.17.1388

Ding X, Du J, Mao K, et al., 2019, MicroRNA-143- 3p Suppresses Tumorigenesis by Targeting Catenin-δ1 in Colorectal Cancer. OncoTargets Ther, 12:3255. DOI: 10.2147/OTT.S184118

Qiu Z, Guo W, Wang Q, et al., 2015, MicroRNA-124 Reduces the Pentose Phosphate Pathway and Proliferation by Targeting PRPS1 and RPIA mRNAs in Human Colorectal Cancer Cells. Gastroenterology, 149:1587–98. DOI: 10.1053/j.gastro.2015.07.050

Liu K, Yao H, Wen Y, et al., 2018, Functional Role of a Long Non-Coding RNA LIFR-AS1/miR-29a/TNFAIP3 Axis in Colorectal Cancer Resistance to Pohotodynamic Therapy. Biochim Biophys Acta, 1864:2871–80. DOI: 10.1016/j. bbadis.2018.05.020

Chen SH, Lin F, Zhu JM, et al., 2021, An Immune-related lncRNA Prognostic Model in Papillary Renal Cell Carcinoma: A lncRNA Expression Analysis. Genomics, 113:531–40. DOI: 10.1016/j.ygeno.2020.09.046

Cheng Z, Wang G, Zhu W, et al., 2020, LEF1-AS1 Accelerates Tumorigenesis in Glioma by Sponging miR- 489-3p to Enhance HIGD1A. Cell Death Dis, 11:1–1. DOI: 10.1038/s41419-020-02823-0

Liu W, Li L, Ye H, et al., 2018, Role of COL6A3 in Colorectal Cancer. Oncol Rep, 39:2527–36. DOI: 10.3892/ or.2018.6331

Le CC, Bennasroune A, Langlois B, et al., 2020, Functional Interplay Between Collagen Network and Cell Behavior within Tumor Microenvironment in Colorectal Cancer. Front Oncol, 10:527. DOI: 10.3389/fonc.2020.00527

Eylem CC, Yilmaz M, Derkus B, et al., 2002, Untargeted Multi-omic Analysis of Colorectal Cancer-specific Exosomes Reveals Joint Pathways of Colorectal Cancer in Both Clinical Samples and Cell Culture. Cancer Lett, 469:186–94. DOI: 10.1016/j.canlet.2019.10.038

Zhu CC, Chen C, Xu ZQ, et al., 2018, CCR6 Promotes Tumor Angiogenesis via the AKT/NF-κB/VEGF Pathway in Colorectal Cancer. Biochim Biophys Acta Mol Basis Dis, 1864:387–97. DOI: 10.1016/j.bbadis.2017.10.033

Jiang M, Xu B, Li X, et al., 2019, Correction: O-GlcNAcylation Promotes Colorectal Cancer Metastasis via the miR-101-O-GlcNAc/EZH2 Regulatory Feedback Circuit. Oncogene, 38:5744–5. DOI: 10.1038/s41388-019- 0834-2

Taipale J, Beachy PA, 2001, The Hedgehog and Wnt Signalling Pathways in Cancer. Nature, 411:349–54. DOI: 10.1038/s41388-019-0834-2

Carraway KL, Hull SR, 19991, Cell Surface Mucin-type Glycoproteins and Mucin-like Domains. Glycobiology, 1:131–8. DOI: 10.1093/glycob/1.2.131

DuRand GE, Seta N, 2000, Protein Glycosylation and Diseases: Blood and Urinary Oligosaccharides as Markers for Diagnosis and Therapeutic Monitoring. Clin Chem, 46:795–805. DOI: 10.1093/clinchem/46.6.795

Huang HC, Klein PS, 2004, The Frizzled Family: Receptors for Multiple Signal Transduction Pathways. Genome Biol, 5:1–7. DOI: 10.1186/gb-2004-5-7-234

Takebe N, Miele L, Harris PJ, et al., 2015, Targeting Notch, Hedgehog, and Wnt Pathways in Cancer Stem Cells: Clinical Update. Nat Rev Clin Oncol, 12:445–64. DOI: 10.1038/nrclinonc.2015.61

Sonderegger S, Husslein H, Leisser C, et al., 2007. Complex Expression Pattern of Wnt Ligands and Frizzled Receptors in Human Placenta and its Trophoblast Subtypes. Placenta, 28:S97–102. DOI: 10.1016/j.placenta.2006.11.003

Hawkins AG, Pedersen EA, Treichel S, et al., 2020, Wnt/ β-catenin-Activated Ewing Sarcoma Cells Promote the Angiogenic Switch. JCI Insight, 5:e135188. DOI: 10.1172/ jci.insight.135188

Van Es JH, Barker N, Clevers H, 2002, You Wnt some, you lose some: Oncogenes in the Wnt Signaling Pathway. Curr Opin Genet Dev, 13:28–33. DOI: 10.1016/S0959- 437X(02)00012-6

Mandati V, 2013, Le Rôle de L’extrémité C-terminale de la Protéine Merline dans sa Fonction Anti-tumorale (Doctoral Dissertation, Paris 11).

Chang TH, Hsieh FL, Zebisch M, et al., 2015, Structure and Functional Properties of Norrin Mimic Wnt for Signalling with Frizzled4, Lrp5/6, and Proteoglycan. Elife, 4:e06554. DOI: 10.7554/eLife.06554.028

Wang IC, Chen YJ, Hughes D, Petrovic V, et al., 2005, Forkhead box M1 Regulates the Transcriptional Network of Genes Essential for Mitotic Progression and Genes Encoding the SCF (Skp2-Cks1) Ubiquitin Ligase. Mol Cell Biol, 25:10875–94. DOI: 10.1128/MCB.25.24.10875-10894.2005

Haegele L, Ingold B, Naumann H, et al., 2003, Wnt Signalling Inhibits Neural Differentiation of Embryonic Stem Cells by Controlling Bone Morphogenetic Protein Expression. Mol Cell Neurosci, 24:696–708. DOI: 10.1016/ S1044-7431(03)00232-X

de Almeida GC, Oliveira LF, Predes D, et al., 2002, Piperine Suppresses the Wnt/β-catenin Pathway and has Anti-cancer Effects on Colorectal Cancer Cells. Sci Rep, 10:1–2. DOI: 10.1038/s41598-020-68574-2

Zhang Y, Wang S, Kang W, et al., 2018, CREPT Facilitates Colorectal Cancer Growth through Inducing Wnt/β- Catenin Pathway by Enhancing p300-mediated β-catenin Acetylation. Oncogene, 37:3485–500. DOI: 10.1038/ s41388-018-0161-z

Zheng G, Li W, Zuo B, et al., 2016, High Expression of CREPT Promotes Tumor Growth and is Correlated with Poor Prognosis in Colorectal Cancer. Biochem Biophys Res Commun, 480:436–42. DOI: 10.1016/j.bbrc.2016.10.067

Qin J, Wen B, Liang Y, et al., 2019, Histone Modifications and their Role in Colorectal Cancer. Pathol Oncol Res, 4:1– 1. DOI: 10.1007/s12253-019-00663-8

Sun K, He SB, Yao YZ, et al., 2019, Tre2 (USP6NL) Promotes Colorectal Cancer Cell Proliferation via Wnt/β- catenin Pathway. Cancer Cell Int, 19:1–2. DOI: 10.1186/ s12935-019-0823-0

Xu C, Tian G, Jiang C, et al., 2019, NPTX2 Promotes Colorectal Cancer Growth and Liver Metastasis by the Activation of the Canonical Wnt/β-Catenin Pathway via FZD6. Cell Death Dis, 10:1–2. DOI: 10.1038/s41419-019- 1467-7

Liu L, Zhang Y, Wong CC, et al., 2018, RNF6 Promotes Colorectal Cancer by Activating the Wnt/β-catenin Pathway via Ubiquitination of TLE3. Cancer Res, 78:1958–71. DOI: 10.1158/0008-5472.CAN-17-2683

Zeng Q, Che Y, Zhang Y, et al., 2020, Thymol Isolated from Thymus vulgaris L. Inhibits Colorectal Cancer Cell Growth and Metastasis by Suppressing the Wnt/β-catenin Pathway. Drug Des Dev Ther, 14:2535. DOI: 10.2147/DDDT.S254218

Zhou F, Xue M, Qin D, et al., HIV-1 Tat Promotes Kaposi’s Sarcoma-Associated Herpesvirus (KSHV) vIL-6-induced Angiogenesis and Tumorigenesis by Regulating PI3K/ PTEN/AKT/GSK-3β Signaling Pathway. PLoS One, 8:e53145. DOI: 10.1371/journal.pone.0053145

Poon HY, Stone JC, 2009, Functional Links between Diacylglycerol and Phosphatidylinositol Signaling Systems in Human Leukocyte-derived Cell Lines. Biochem Biophys Res Commun, 390:1395–401. DOI: 10.1016/j. bbrc.2009.11.004

Mattson MP, Culmsee C, Yu ZF, 2000, Apoptotic and Antiapoptotic Mechanisms in Stroke. Cell Tissue Res, 301:173–87. DOI: 10.1007/s004419900154

Ganeshan TK, 2019, Investigating the Protective Role of the Natural Hormone Melatonin, in Reducing Drug-induced Cardiotoxicity in the Therapy of Chronic Diseases (Doctoral Dissertation, University of Westminster).

Ye M, Zhang Y, Zhang X, et al., 2017, Targeting FBW7 as a Strategy to Overcome Resistance to Targeted Therapy in Non-Small Cell Lung Cancer. Cancer Res, 77:3527–39. DOI: 10.1158/0008-5472.CAN-16-3470

Liu G, Zhou J, Dong M, 2019, Down-regulation of miR-543 Expression Increases the Sensitivity of Colorectal Cancer Cells to 5-Fluorouracil through the PTEN/PI3K/AKT Pathway. Biosci Rep, 39:BSR20190249. DOI: 10.1042/BSR20190249

Liu H, Wang J, Tao Y, et al., 2019, Curcumol Inhibits Colorectal Cancer Proliferation by Targeting miR-21 and Modulated PTEN/PI3K/Akt Pathways. Life Sci, 221:354– 61. DOI: 10.1016/j.lfs.2019.02.049

Alaaeddine RA, Elzahhar PA, AlZaim I, et al., 2021, The Emerging Role of COX-2, 15-LOX and PPARγ in Metabolic Diseases and Cancer: An Introduction to Novel Multi-target Directed Ligands (MTDLs). Curr Med Chem, 28:2260–300. DOI: 10.2174/0929867327999200820173853

Ma J, Sun X, Wang Y, et al., 2019, Fibroblast-derived CXCL12 Regulates PTEN Expression and is Associated with the Proliferation and Invasion of Colon Cancer Cells via PI3k/Akt Signaling. Cell Commun Signaling, 2019 Dec;17(1):1–2. DOI: 10.1186/s12964-019-0432-5

Yin X, Liu Z, Zhu P, et al., 2019, CXCL12/CXCR4 Promotes Proliferation, Migration, and Invasion of Adamantinomatous Craniopharyngiomas via PI3K/ AKT Signal Pathway. J Cell Biochem, 120:9724–36. DOI: 10.1002/jcb.28253

Cheng H, Jiang X, Zhang Q, et al., 2020, Naringin Inhibits Colorectal Cancer Cell Growth by Repressing the PI3K/ AKT/mTOR Signaling Pathway. Exp Ther Med, 19:3798– 804. DOI: 10.3892/etm.2020.8649

Sui X, Kong N, Ye L, et al., 2014, p38 and JNK MAPK Pathways Control the Balance of Apoptosis and Autophagy in Response to Chemotherapeutic Agents. Cancer Lett, 344:174–9. DOI: 10.1016/j.canlet.2013.11.019

Hackel PO, Zwick E, Prenzel N, et al., 1999, Epidermal Growth Factor Receptors: Critical Mediators of Multiple Receptor Pathways. Curr Opin Cell Biol, 11:184–9. DOI: 10.1016/S0955-0674(99)80024-6

Segmüller N, Ellendorf U, Tudzynski B, et al., 2007, BcSAK1, a Stress-Activated Mitogen-activated Protein Kinase, is Involved in Vegetative Differentiation and Pathogenicity in Botrytis cinerea. Eukaryotic Cell, 6:211– 21. DOI: 10.1128/EC.00153-06

Widmann C, Gibson S, Jarpe MB, et al., 1999, Mitogen-activated Protein Kinase: Conservation of a Three-kinase Module from Yeast to Human. Physiol Rev, 79:143–80. DOI: 10.1152/physrev.1999.79.1.143

Rose BA, Force T, Wang Y, 2010, Mitogen-activated Protein Kinase Signaling in the Heart: Angels Versus Demons in a Heart-breaking Tale. Physiol Rev, 90:1507–46. DOI: 10.1152/physrev.00054.2009

Keyse SM, 2000, Protein Phosphatases and the Regulation of Mitogen-Activated Protein Kinase Signalling. Curr Opin Cell Biol, 12:186–92. DOI: 10.1016/S0955-0674(99)00075-7

Orban PC, Chapman PF, Brambilla R, 1999, Is the Ras-MAPK Signalling Pathway Necessary for Long-term Memory Formation? Trends Neurosci, 22:38–44. DOI: 10.1016/S0166-2236(98)01306-X

Severin S, Ghevaert C, Mazharian A, 2010, The Mitogen‐activated Protein Kinase Signaling Pathways: Role in Megakaryocyte Differentiation. J Thromb Haemost, 8:17– 26. DOI: 10.1111/j.1538-7836.2009.03658.x

Morandell S, Stasyk T, Skvortsov S, et al., 2008, Quantitative Proteomics and Phosphoproteomics Reveal Novel Insights into Complexity and Dynamics of the EGFR Signaling Network. Proteomics, 8:4383–401. DOI: 10.1002/pmic.200800204

Preisinger C, Von Kriegsheim A, Matallanas D, et al., 2008, Proteomics and Phosphoproteomics for the Mapping of Cellular Signalling Networks. Proteomics, 8:4402–15. DOI: 10.1002/pmic.200800136

Peschard P, Fournier TM, Lamorte L, et al., 2001, Mutation of the c-Cbl TKB Domain Binding Site on the Met Receptor Tyrosine Kinase Converts it into a Transforming Protein. Mol Cell, 8:995–1004. DOI: 10.1016/S1097- 2765(01)00378-1

Marmor MD, Yarden Y, 2004, Role of Protein Ubiquitylation in Regulating Endocytosis of Receptor Tyrosine Kinases. Oncogene, 23:2057–70. DOI: 10.1038/sj.onc.1207390

Feller SM, Lewitzky M, 2006, Potential Disease Targets for Drugs that Disrupt Protein-protein Interactions of Grb2 and Crk Family Adaptors. Curr Pharm Des, 12:529–48. DOI: 10.2174/138161206775474369

Schneekloth AR, 2009, Development of Proteolysis Targeting Chimeric Molecules (PROTACs) and Studies on the Biological Activity of Tyroscherin. Yale University.

Claperon A, Therrien M, 2007, KSR and CNK: Two Scaffolds Regulating RAS-mediated RAF Activation. Oncogene, 26:3143–58. DOI: 10.1038/sj.onc.1210408

Kolch W, 2000, Meaningful Relationships: The Regulation of the Ras/Raf/MEK/ERK Pathway by Protein Interactions. Biochem J, 351:289–305. DOI: 10.1042/bj3510289

Cato AR, 2013, The Effects of Hexabromocyclododecane (HBCD) and Tetrabromobisphenol A (TBBPA) on Mitogen-activated Protein Kinases in Human Natural Killer Cells (Doctoral Dissertation, Tennessee State University).

Downward J, 20003, Targeting RAS Signalling Pathways in Cancer Therapy. Nat Rev Cancer, 3:11–22. DOI: 10.1038/ nrc969

Hilger RA, Scheulen ME, Strumberg D, 2002, The Ras- Raf-MEK-ERK Pathway in the Treatment of Cancer. Oncol Res Treatment, 25:511–8. DOI: 10.1159/000068621

Attar-Schneider O, Drucker L, Zismanov V, et al., 2021, Bevacizumab Attenuates Major Signaling Cascades and eIF4E Translation Initiation Factor in Multiple Myeloma Cells. Lab Investig, 92:178–90. DOI: 10.1038/ labinvest.2011.162

Zhao YL, Zhong SR, Zhang SH, et al., 2019, UBN2 Promotes Tumor Progression via the Ras/MAPK Pathway and Predicts Poor Prognosis in Colorectal Cancer. Cancer Cell Int, 19:126. DOI: 10.1186/s12935-019-0848-4

Tang B, Liang W, Liao Y, et al., 2019, PEA15 Promotes Liver Metastasis of Colorectal Cancer by Upregulating the ERK/MAPK Signaling Pathway. Oncol Rep, 41:43–56. DOI: 10.3892/or.2018.6825

Hindupur SK, Balaji SA, Saxena M, et al., 2014, Identification of a Novel AMPK-PEA15 Axis in the Anoikis-resistant Growth of Mammary Cells. Breast Cancer Res, 16:1–6. DOI: 10.1186/s13058-014-0420-z

Angius A, Pira G, Scanu AM, et al., 2019, MicroRNA- 425-5p Expression Affects BRAF/RAS/MAPK Pathways in Colorectal Cancers. Int J Med Sci, 16:1480–91. DOI: 10.7150/ijms.35269

Ponsioen B, Post JB, des Amorie JR, et al., 2021, Quantifying Single-cell ERK Dynamics in Colorectal Cancer Organoids Reveals EGFR as an Amplifier of Oncogenic MAPK Pathway Signalling. Nat Cell Biol, 23:377–90. DOI: 10.1038/s41556-021-00654-5

Mellado M, Rodríguez‐Frade JM, Vila‐Coro AJ, et al., 2001, Chemokine Receptor Homo‐or Heterodimerization Activates Distinct Signaling Pathways. EMBO J, 20:2497– 507. DOI: 10.1093/emboj/20.10.2497

Goel A, Singh S, 2020, Emerging Approaches for the Treatment of Alzheimer Disease: Targeting NF-κB Pathway. DOI: 10.22541/au.159493419.94920936

Bu Y, 2014, Phosphorylation of NF-κB RelA/p65 on Ser536 Signals Cancer Cells TO Death and Enhances Chemosensitivity. Southern Illinois University at Carbondale.

Majdalawieh AF, Zhang L, Fuki IV, 2006, Adipocyte Enhancer-binding Protein-1 (AEBP1) is a Novel Player in Macrophage Cholesterol Homeostasis, Inflammation, and Atherogenesis. Proc Natl Acad Sci U S A, 103:2346–51. DOI: 10.1073/pnas.0508139103

Bose D, 2002, Human Herpesvirus K1 Open Reading Frame Activates NFκB and Contributes to the Inflammatory Phenotype. University of Maryland, Baltimore.

Kannathasan T, Kuo WW, Chen MC, et al., 2020, Chemoresistance-Associated Silencing of miR-4454 Promotes Colorectal Cancer Aggression through the GNL3L and NF-κB Pathway. Cancers, 12:1231. DOI: 10.3390/ cancers12051231

Liu W, Wang S, Sun Q, et al., 2018, DCLK1 Promotes Epithelial‐Mesenchymal Transition via the PI3K/Akt/NF‐ κB Pathway in Colorectal Cancer. Int J Cancer, 142:2068– 79. DOI: 10.1002/ijc.31232

Westphalen CB, Quante M, Wang TC, 2017, Functional Implication of Dclk1 and Dclk1- expressing Cells in Cancer. Small GTPases, 8:164–71. DOI: 10.1080/21541248.2016.1208792

Makino S, Takahashi H, Okuzaki D, et al., 2020, DCLK1 Integrates Induction of TRIB3, EMT, Drug Resistance and Poor Prognosis in Colorectal Cancer. Carcinogenesis, 41:303–12. DOI: 10.1093/carcin/bgz157

Chen C, Xu ZQ, Zong YP, et al., 2019, CXCL5 Induces Tumor Angiogenesis via Enhancing the Expression of FOXD1 Mediated by the AKT/NF-κB Pathway in Colorectal Cancer. Cell Death Dis, 10:1–5. DOI: 10.1038/s41419-019-1431-6

Wang H, Yao L, Gong Y, et al., 2018, TRIM31 Regulates Chronic Inflammation via NF-κB Signal Pathway to Promote Invasion and Metastasis in Colorectal Cancer. Am J Transl Res, 10:1247.

Huang L, Wang X, Wen C, et al., 2015, Hsa-miR-19a is Associated with Lymph Metastasis and Mediates the TNF-α Induced Epithelial-to-Mesenchymal Transition in Colorectal Cancer. Sci Rep, 5:1–2. DOI: 10.1038/srep13350

Lin SY, Li TY, Liu Q, et al., 2012, GSK3-TIP60-ULK1 Signaling Pathway Links Growth Factor Deprivation to Autophagy. Science, 336:477–81. DOI: 10.1126/science.1217032

Toyota M, Ahuja N, Ohe-Toyota M, et al., 1999, CpG Island Methylator Phenotype in Colorectal Cancer. Proc Natl Acad Sci, 96:8681–6. DOI: 10.1073/pnas.96.15.8681

Retsky M, Demicheli R, Hrushesky W, et al., 2010, Surgery Triggers Outgrowth of Latent Distant Disease in Breast Cancer: An Inconvenient Truth? Cancers, 2:305–37. DOI: 10.3390/cancers2020305

Ahmed FE, 20003, Colon Cancer: Prevalence, Screening, Gene Expression and Mutation, and Risk Factors and Assessment. J Environ Sci Health Part C, 21:65–131. DOI: 10.1081/GNC–120026233

Miller EC, Miller JA, 1983, Charles Heidelberger 1920- 1983. Cancer, 43, 155.

Heidelberger C, Chaudhuri NK, Danneberg P, et al., 1957, Fluorinated Pyrimidines, a New Class of Tumour-inhibitory Compounds. Nature, 179:663–6. DOI: 10.1038/179663a0

Sethy C, Kundu CN, 2021, 5-Fluorouracil (5-FU) Resistance and the New Strategy to Enhance the Sensitivity against Cancer: Implication of DNA Repair Inhibition. Biomed Pharmacother, 137:111285. DOI: 10.1016/j. biopha.2021.111285

Plà Solans H, 2014, Design, Synthesis and Biological Evaluation of New Polymer-Drug Conjugates Based on Polyglutamic Acid and 5-Fluorouracil for the Treatment of Advanced Colorectal Cancer (Doctoral Dissertation, Universitat de Barcelona).

Schaffer S, 2018, Exploiting the Overexpression of CYP2A6 in Colon Cancer with the 5-Fluorouracil Prodrug, Tegafur (Doctoral Dissertation, University of the Sciences in Philadelphia).

Vodenkova S, Buchler T, Cervena K, et al., 2020, 5-fluorouracil and other Fluoropyrimidines in Colorectal Cancer: Past, Present and Future. Pharmacol Ther, 206:107447. DOI: 10.1016/j.pharmthera.2019.107447

Ndreshkjana B, Çapci A, Klein V, et al., 2019, Combination of 5-Fluorouracil and Thymoquinone Targets Stem Cell Gene Signature in Colorectal Cancer Cells. Cell Death Dis, 10:1–6. DOI: 10.1038/s41419-019-1611-4

Malet-Martino M, Martino R, 2002, Oncologist Clinical Studies of three Oral Prodrugs of 5-fluorouracil. Oncologiest, 7:288–323. DOI:10.1634/theoncologist.7-4-288

Petty RD, Cassidy J, 2004, Novel Fluoropyrimidines: Improving the Efficacy and Tolerability of Cytotoxic Therapy. Curr Cancer Drug Targets, 4:191–204. DOI: 10.2174/1568009043481533

Perrain V, Bihan K, Bompaire F, et al., 2021, Leukoencephalopathy with Transient Splenial Lesions Related to 5‐Fluorouracil or Capecitabine. Eur J Neurol, 28:2396–402. DOI: 10.1111/ene.14857

Twelves CJ, 2006, X-ACT Investigators. Xeloda® in Adjuvant Colon Cancer Therapy (X-ACT) Trial: Overview of Efficacy, Safety, and Cost-effectiveness. Clin Colorectal Cancer, 6:278–87. DOI: 10.3816/CCC.2006.n.046

Chan SL, Chan AW, Mo F, et al., 2018, Association between Serum Folate Level and Toxicity of Capecitabine During Treatment for Colorectal Cancer. Oncologist, 23:1436. DOI: 10.1634/theoncologist.2017-0637

Sriram D, Yogeeswari P, Thirumurugan R, et al., 2005, Camptothecin and its Analogues: A Review on their Chemotherapeutic Potential. Nat Prod Res, 19:393–412. DOI: 10.1080/14786410412331299005

Feun L, Savaraj N, 2008, Topoisomerase I Inhibitors for the Treatment of Brain Tumors. Expert Rev Anticancer Ther, 8:707–16. DOI: 10.1586/14737140.8.5.707

Tanabe K, Ikegami Y, Ishida R, et al., 1991, Inhibition of Topoisomerase II by Antitumor Agents bis (2, 6-dioxopiperazine) Derivatives. Cancer Res, 51:4903–8.

Scarabel L, Garziera M, Fortuna S, et al., 2020, Soluble HLA-G Expression Levels and HLA-G/irinotecan Association in Metastatic Colorectal Cancer Treated with Irinotecan-based Strategy. Sci Rep, 10:1–1. DOI: 10.1038/ s41598-020-65424-z

Pendyala L, Creaven PJ, 1993, In Vitro Cytotoxicity, Protein Binding, Red Blood Cell Partitioning, and Biotransformation of Oxaliplatin. Cancer Res, 53:5970–6.

Asadzadeh Z, Mansoori B, Mohammadi A, et al., 2019, microRNAs in Cancer Stem Cells: Biology, Pathways, and Therapeutic Opportunities. J Cell Physiol, 234:10002–17. DOI: 10.1002/jcp.27885

Wang Q, Chen X, Jiang Y, et al., 2020, Elevating H3K27me3 Level Sensitizes Colorectal Cancer to Oxaliplatin. J Mol Cell Biol, 12:125–37. DOI: 10.1093/jmcb/mjz032

Madigan JP, Robey RW, Poprawski JE, et al., 2020, A Role for Ceramide Glycosylation in Resistance to Oxaliplatin in Colorectal Cancer. Exp Cell Res, 388:111860. DOI: 10.1016/j.yexcr.2020.111860

Leahy KM, Koki AT, Masferrer JL, 200, Role of Cyclooxygenases in Angiogenesis. Curr Med Chem, 7:1163–70. DOI: 10.2174/0929867003374336

Chaplain MA, 1996, Avascular Growth, Angiogenesis and Vascular Growth in Solid Tumours: The Mathematical Modelling of the Stages of Tumour Development. Math Comput Model, 23:47–87. DOI: 10.1016/0895-7177(96)00019-2

Neufeld G, Cohen T, Gengrinovitch S, et al., 1999, Vascular Endothelial Growth Factor (VEGF) and its Receptors. FASEB J, 13:9–22. DOI: 10.1096/fasebj.13.1.9

Shinkaruk S, Bayle M, Lain G, et al., 2003, Vascular Endothelial Cell Growth Factor (VEGF), an Emerging Target for Cancer Chemotherapy. Curr Med Chem Anticancer Agents, 3:95–117. DOI: 10.2174/1568011033353452

Ferrara N, Hillan KJ, Novotny W, 2005, Bevacizumab (Avastin), a Humanized Anti-VEGF Monoclonal Antibody for Cancer Therapy. Biochem Biophys Res Commun, 333:328–35. DOI: 10.1016/j.bbrc.2005.05.132

Shen Y, Wang X, Lu J, et al., 2020, Reduction of Liver Metastasis Stiffness Improves Response to Bevacizumab in Metastatic Colorectal Cancer. Cancer Cell, 37:800–17. DOI: 10.1016/j.ccell.2020.05.005

Artaç M, Korkmaz L, Coşkun HŞ, et al., 2019, Bevacuzimab may be Less Effective in Obese Metastatic Colorectal Cancer Patients. J Gastrointestinal Cancer, 50:214–20. DOI: 10.1007/s12029-017-0047-2

Dent P, Reardon DB, Park JS, et al., 1999, Radiation-induced Release of Transforming Growth Factor α Activates the Epidermal Growth Factor Receptor and Mitogen-activated Protein Kinase Pathway in Carcinoma Cells, Leading to Increased Proliferation and Protection from Radiation-induced Cell Death. Mol Biol Cell, 10:2493–506. DOI: 10.1091/mbc.10.8.2493

Tinhofer I, Klinghammer K, Weichert W, et al., 2011, Expression of Amphiregulin and EGFRvIII affect Outcome of Patients with Squamous Cell Carcinoma of the Head and Neck Receiving Cetuximab-Docetaxel Treatment. Clin Cancer Res, 17:5197–204. DOI: 10.1158/1078-0432.CCR- 10-3338

Dokala A, Thakur SS, 2017, Extracellular Region of Epidermal Growth Factor Receptor: A Potential Target for Anti-EGFR Drug Discovery. Oncogene, 36:2337–44. DOI: 10.1038/onc.2016.393

Roskoski R Jr., 2019, Small Molecule Inhibitors Targeting the EGFR/ErbB Family of Protein-tyrosine Kinases in Human Cancers. Pharmacol Res, 139:395–411. DOI: 10.1016/j.phrs.2018.11.014

Humblet Y, 2004, Cetuximab: An IgG1 Monoclonal Antibody for the Treatment of Epidermal Growth Factor Receptor-expressing Tumours. Expert Opin Pharmacother, 5:1621–33. DOI: 10.1517/14656566.5.7.1621

Fakih M, Vincent M, 2010, Adverse Events Associated with Anti-EGFR Therapies for the Treatment of Metastatic Colorectal Cancer. Curr Oncol, 17 Suppl 1:S18. DOI: 10.3747/co.v17is1.615

Mao C, Zeng X, Zhang C, et al., 2021, Mechanisms of Pharmaceutical Therapy and Drug Resistance in Esophageal Cancer. Front Cell Dev Biol, 9:22. DOI: 10.3389/ fcell.2021.612451

Sabra R, Billa N, Roberts CJ, 2019, Cetuximab-conjugated Chitosan-pectinate (Modified) Composite Nanoparticles for Targeting Colon Cancer. Int J Pharm, 572:118775. DOI: 10.1016/j.ijpharm.2019.118775

Kopetz S, Chang GJ, Overman MJ, et al., 2009, Improved Survival in Metastatic Colorectal Cancer is Associated with Adoption of Hepatic Resection and Improved Chemotherapy. J Clin Oncol, 27:3677. DOI: 10.1200/ JCO.2008.20.5278

Price TJ, Peeters M, Kim TW, et al., 2014, Panitumumab Versus Cetuximab in Patients with Chemotherapy-refractory Wild-type KRAS Exon 2 Metastatic Colorectal Cancer (ASPECCT): A Randomised, Multicentre, Open-Label, Non-Inferiority Phase 3 Study. Lancet Oncol, 15:569–79. DOI: 10.1016/S1470-2045(14)70118-4

Carrato A, 2008, Adjuvant Treatment of Colorectal Cancer. Gastrointest Cancer Res, 2 4 Suppl 2:S42.

Beets-Tan RG, Beets GL, Vliegen RF, et al., 2001, Accuracy of Magnetic Resonance Imaging in Prediction of Tumour-free Resection Margin in Rectal Cancer Surgery. Lancet, 357:497–504. DOI: 10.1016/S0140-6736(00)04040-X

Rödel C, Graeven U, Fietkau R, et al., 2015, Oxaliplatin Added to Fluorouracil-based Preoperative Chemoradiotherapy and Postoperative Chemotherapy of Locally Advanced Rectal Cancer (the German CAO/ARO/ AIO-04 study): Final Results of the Multicentre, Open-label, Randomised, Phase 3 Trial. Lancet Oncol, 16:979– 89. DOI: 10.1016/S1470-2045(15)00159-X

Sobrero A, Köhne CH, 2006, Should Adjuvant Chemotherapy become Standard Treatment for Patients with Stage II Colon Cancer? Lancet Oncol, 7:515–7. DOI: 10.1016/S1470-2045(06)70727-6

Evrard C, Tachon G, Randrian V, et al., 2019, Microsatellite Instability: Diagnosis, Heterogeneity, Discordance, and Clinical Impact in Colorectal Cancer. Cancers, 111567. DOI: 10.3390/cancers11101567

Bond CE, Nancarrow DJ, Wockner LF, et al., 2014, Microsatellite Stable Colorectal Cancers Stratified by the BRAF V600E Mutation Show Distinct Patterns of Chromosomal Instability. PLoS One, 9:e91739. DOI: 10.1371/journal.pone.0091739

Jain RK, 2002, Tumor Angiogenesis and Accessibility: Role of Vascular Endothelial Growth Factor. Semin Oncol, 29:3–9. DOI: 10.1016/S0093-7754(02)70063-8

Bosset JF, Collette L, Calais G, et al., 2006, Chemotherapy with Preoperative Radiotherapy in Rectal Cancer. N Engl J Med, 355:1114–23. DOI: 10.1056/ NEJMoa060829

Bosset JF, Bosset M, Nguyen F, et al., 2008, Defining Preoperative Treatment Strategies in t3 Rectal Cancer. Gastrointest Cancer Res, 2 4 Suppl: S54–7.