Deciphering Colorectal Cancer Development: From Genomic and Metabolic Perspectives to Innovative Diagnostic Approaches and Nanotechnology-Based Management Strategies
https://doi.org/10.22416/1382-4376-2025-35-3-7-20
Abstract
Aim. To explore the various aspects of colorectal cancer with its correlation with human lifestyles and the inherited genetic makeup and its related metabolism. To understand the various diagnostic patterns, and to explore the nanotechnology-based combined diagnostic and therapeutic methods.
Key points. Colorectal cancer grades as the third most frequently identified malignancy, alongside being the chief cause of cancer related fatalities globally. The modification of normal colonic mucosal lining into a malignant one, as an outcome of collection of many genetic and epigenetic modifications contributes to the colorectal carcinogenesis. However, lifestyle changes have a significant role to play in this. An accumulation of metabolic disorders, the metabolic syndrome, which induces the dysregulation of prime biomolecules are one of the significant factors that induce carcinogenic effects in the normal colonocytes leading to the colorectal carcinogenesis. Non-alcoholic fatty liver disease, also termed as the hepatic expression of metabolic syndrome, is a prime threat for the incidence of colorectal cancer. It induces the malignancy by encouraging secretion of proinflammatory cytokines. As the number of mechanisms leading to colorectal cancer are rising, novel diagnostic tools for the early screening of the cancer are being introduced, and better techniques are still under research. Many studies have indicated the decrease in occurrence and fatalities linked to this disease, which can be attributed to the well-developed screening techniques in cancer management. Nanotechnology, under the area of colorectal cancer management, has improved the screening and delivery of drugs for cancer treatment procedures attributing to its excellent bioimaging and drug encapsulation properties.
Conclusion. This article will review the various genomic and lifestyle interventions affecting the progression of colorectal carcinogenesis. Additionally, we will review the novel and future theranostic techniques available for the management of colorectal cancer.
Keywords
About the Authors
Sh. A. RaoIndia
Shruthi A. Rao — Bachelor of Science in Chemistry and Zoology, Undergraduate Student
560027, Lal Bagh Main Rd, 36, Langford Gardens, Bengaluru, Karnataka, India.
V. Varenya
India
Vithur Varenya — Master of Science in Zoology, Postgraduate Student
560027, Lal Bagh Main Rd, 36, Langford Gardens, Bengaluru, Karnataka, India
H. S. Samanvitha
India
Samanvitha H.S. — Bachelor of Science in Chemistry and Zoology, Undergraduate Student
560027, Lal Bagh Main Rd, 36, Langford Gardens, Bengaluru, Karnataka, India
S. N. Prasad
India
Sinchana N. Prasad — Bachelor of Science in Chemistry and Zoology, Undergraduate Student
560027, Lal Bagh Main Rd, 36, Langford Gardens, Bengaluru, Karnataka, India
K. A. Paari
India
Kuppusamy Alagesan Paari — PhD, Dr., Assistant Professor at the Department of Life Sciences
560029, Hosur Main Rd, Bhavani Nagar, Post, Bengaluru, Karnataka, India
J. A. George
India
Jincy A. George — PhD, Dr., Assistant Professor at the Department of Biology, School of Life Sciences
560027, Lal Bagh Main Rd, 36, Langford Gardens, Bengaluru, Karnataka, India
References
1. National Cancer Institute. Cancer Biology Research. 2023. URL: https://www.cancer.gov
2. Sung J.J.Y., Chiu H.M., Jung K.W., Jun J.K., Sekiguchi M., Matsuda T., et al. Increasing trend in young-onset colorectal cancer in Asia: More cancers in men and more rectal cancers. Am J Gastroenterol. 2019;114(22):322–9. DOI: 10.14309/ajg.0000000000000133
3. Sharma S., Bhattacharya S., Joshi K., Singh S. A shift in focus towards precision oncology, driven by revolutionary nanodiagnostics; revealing mysterious pathways in colorectal carcinogenesis. J Cancer Res Clin Oncol. 2023;149(17):16157–77. DOI: 10.1007/s00432-023-05331-8
4. Rubio C.A. Three pathways of colonic carcinogenesis in rats. Anticancer Res. 2017;37(1):15–20. DOI: 10.21873/anticanres.11284
5. Abolghasemi Fard A., Mahmoodzadeh A. Unraveling the progression of colon cancer pathogenesis through epigenetic alterations and genetic pathways. Cureus. 2024;16(5):e59503. DOI: 10.7759/cureus.59503
6. Harada S., Morlote D. Molecular pathology of colorectal cancer. Adv Anat Pathol. 2020;27(1):20–6. DOI: 10.1097/PAP.0000000000000247
7. Shen X., Wang Y., Zhao R., Wan Q., Wu Y., Zhao L., et al. Metabolic syndrome and the risk of colorectal cancer: A systematic review and meta-analysis. Int J Colorectal Dis. 2021;36(10):2215–25. DOI: 10.1007/s00384-021-03974-y
8. Lu B., Qian J.-M., Li J.-N. The metabolic syndrome and its components as prognostic factors in colorectal cancer: A meta-analysis and systematic review. J Gastroenterol Hepatol. 2023;38(2):187–96. DOI: 10.1111/jgh.16042
9. Chen H., Zheng X., Zong X., Li Z., Li N., Hur J., et al. Metabolic syndrome, metabolic comorbid conditions and risk of early-onset colorectal cancer. Gut. 2021;70(6):1147–54. DOI: 10.1136/gutjnl-2020-321661
10. Xing Q.Q., Li J.M., Chen Z.J., Lin X.Y., You Y.Y., Hong M.Z., et al. Global burden of common cancers attributable to metabolic risks from 1990 to 2019. Med. 2023;4(3):168–81. DOI: 10.1016/j.medj.2023.02.002
11. Oliveira M.L., Biggers A., Oddo V.M., Yanez B., Booms E., Sharp L., et al. A perspective review on diet quality, excess adiposity, and chronic psychosocial stress and implications for early-onset colorectal cancer. J Nutr. 2024;154(4):1069–79. DOI: 10.1016/j.tjnut.2024.03.002
12. Nouri-Vaskeh M., Hashemi P., Hataminia N., Yazdani Y., Nasirian M., Alizadeh L. The impact of piperine on the metabolic conditions of patients with NAFLD and early cirrhosis: A randomized double-blind controlled trial. Sci Rep. 2024;14(1):1053. DOI: 10.1038/s41598-024-51726-z
13. Krause C., Britsemmer J.H., Bernecker M., Molenaar A., Taege N., Lopez-Alcantara N., et al. Liver microRNA transcriptome reveals miR-182 as link between type 2 diabetes and fatty liver disease in obesity. Elife. 2024;12:RP92075. DOI: 10.7554/eLife.92075
14. Yetim A., Şahin M., Kandemir İ., Bulakçı B., Aksakal M.T., Karapınar E., et al. Evaluation of the ability of insulin resistance and lipid-related indices to predict the presence of NAFLD in obese adolescents. Lipids Health Dis. 2024;23(1):208. DOI: 10.1186/s12944-024-02144-7
15. Zhu M., Pu J., Zhang T., Shao H., Su R., Tang C. Inhibiting TRIM8 alleviates adipocyte inflammation and insulin resistance by regulating the DUSP14/MAPKs pathway. Adipocyte. 2024;13(1):2381262. DOI: 10.1080/21623945.2024.2381262
16. Zygulska A.L., Pierzchalski P. Novel diagnostic biomarkers in colorectal cancer. Int J Mol Sci. 2022;23(2):852. DOI: 10.3390/ijms23020852
17. Tao X.Y., Li Q.Q., Zeng Y. Clinical application of liquid biopsy in colorectal cancer: Detection, prediction, and treatment monitoring. Mol Cancer. 2024;23(1):145. DOI: 10.1186/s12943-024-02063-2
18. Kasi P.B., Mallela V.R., Ambrozkiewicz F., Trailin A., Liška V., Hemminki K. Theranostics nanomedicine applications for colorectal cancer and metastasis: Recent advances. Int J Mol Sci. 2023;24(9):7922. DOI: 10.3390/ijms24097922
19. Yamagishi H., Kuroda H., Imai Y., Hiraishi H. Molecular pathogenesis of sporadic colorectal cancers. Chin J Cancer. 2016;35:4. DOI: 10.1186/s40880-015-0066-y
20. Luo C., Zhang H. The role of proinflammatory pathways in the pathogenesis of colitis-associated colorectal cancer. Mediators Inflamm. 2017;2017:5126048. DOI: 10.1155/2017/5126048
21. Nguyen L.H., Goel A., Chung D.C. Pathways of colorectal carcinogenesis. Gastroenterology. 2020;158(2):291–302. DOI: 10.1053/j.gastro.2019.08.059
22. Wielandt A.M., Hurtado C., Moreno C.M., Villarroel C., Castro M., Estay M., et al. Characterization of Chilean patients with sporadic colorectal cancer according to the three main carcinogenic pathways: Microsatellite instability, CpG island methylator phenotype and chromosomal instability. Tumour Biol. 2020;42(7):1010428320938492. DOI: 10.1177/1010428320938492
23. Jasmine F., Haq Z., Kamal M., Raza M., da Silva G., Gorospe K., et al. Interaction between microsatellite instability (MSI) and tumor DNA methylation in the pathogenesis of colorectal carcinoma. Cancers (Basel). 2021;13(19):4956. DOI: 10.3390/cancers13194956
24. Lakhe R., Doshi R., Doshi P., Patil A., Nimbargi R. Assessing mismatch repair expression by immunohistochemistry in colorectal adenocarcinoma — insight from a tertiary care centre. Gulf J Oncolog. 2024;1(45):35–41.
25. Mezzapesa M., Losurdo G., Celiberto F., Rizzi S., d’Amati A., Piscitelli D., et al. Serrated colorectal lesions: An up-to-date review from histological pattern to molecular pathogenesis. Int J Mol Sci. 2022;23(8):4461. DOI: 10.3390/ijms23084461
26. Basyigit S., Uzman M., Kefeli A., Sapmaz F.P., Yeniova A.O., Nazligul Y., et al. Absence of non-alcoholic fatty liver disease in the presence of insulin resistance is a strong predictor for colorectal carcinoma. Int J Clin Exp Med. 2015;8(10):18601–10.
27. Tran T.T., Gunathilake M., Lee J., Kim J. Association between metabolic syndrome and its components and incident colorectal cancer in a prospective cohort study. Cancer. 2022;128(6):1230–41. DOI: 10.1002/cncr.34027
28. Han F., Wu G., Zhang S., Zhang J., Zhao Y., Xu J. The association of metabolic syndrome and its components with the incidence and survival of colorectal cancer: A systematic review and meta-analysis. Int J Biol Sci. 2021;17(2):487–97. DOI: 10.7150/ijbs.52452
29. Lee J.H., Lee K.S., Kim H., Jeong H., Choi M.J., Yoo H.W., et al. The relationship between metabolic syndrome and the incidence of colorectal cancer. Environ Health Prev Med. 2020;25(1):6. DOI: 10.1186/s12199-020-00845-w
30. He Q., Zhang H., Yao S., Zhu D., Lv D., Cui P. A study on relationship between metabolic syndrome and colorectal cancer. J BUON. 2018;23(5):1362–8.
31. Murphy N., Carreras-Torres R., Song M., Chan A.T., Martin R.M., Papadimitriou N., et al. Circulating levels of insulin-like growth factor 1 and insulin-like growth factor binding protein 3 associate with risk of colorectal cancer based on serologic and mendelian randomization analyses. Gastroenterology. 2020;158(5):1300–12e20. DOI: 10.1053/j.gastro.2019.12.020
32. Huang B.L., Wei L.F., Lin Y.W., Huang L.S., Qu Q.Q., Li X.H., et al. Serum IGFBP-1 as a promising diagnostic and prognostic biomarker for colorectal cancer. Sci Rep. 2024;14(1):1839. DOI: 10.1038/s41598-024-52220-2
33. Riedl J.M., Posch F., Moik F., Bezan A., Szkandera J., Smolle M.A., et al. Inflammatory biomarkers in metastatic colorectal cancer: Prognostic and predictive role beyond the first line setting. Oncotarget. 2017;8(56):96048–61. DOI: 10.18632/oncotarget.21647
34. Giby V.G., Ajith T.A. Role of adipokines and peroxisome proliferator-activated receptors in nonalcoholic fatty liver disease. World J Hepatol. 2014;6(8):570–9. DOI: 10.4254/wjh.v6.i8.570
35. Sanna C., Rosso C., Marietti M., Bugianesi E. Nonalcoholic fatty liver disease and extra-hepatic cancers. Int J Mol Sci. 2016;17(5):717. DOI: 10.3390/ijms17050717
36. National Cancer Institute. How fatty liver disease helps cancer thrive in the liver. 2023. URL: https://www.cancer.gov
37. Chakraborty D., Wang J. Nonalcoholic fatty liver disease and colorectal cancer: Correlation and missing links. Life Sci. 2020;262:118507. DOI: 10.1016/j.lfs.2020.118507
38. Mikolasevic I., Orlic L., Stimac D., Hrstic I., Jakopcic I., Milic S. Non-alcoholic fatty liver disease and colorectal cancer. Postgrad Med J. 2016;93(1097):153–8. DOI: 10.1136/postgradmedj-2016-134383
39. Chen W., Wang M., Jing X., Wu C., Zeng Y., Peng J., et al. High risk of colorectal polyps in men with nonalcoholic fatty liver disease: A systematic review and metaanalysis. J Gastroenterol Hepatol. 2020;35(12):2051–65. DOI: 10.1111/jgh.15158
40. Wong M.C.S., Ching J.Y.L., Chan V.C.W., Lam T.Y.T., Luk A.K.C., Wong S.H., et al. Screening strategies for colorectal cancer among patients with nonalcoholic fatty liver disease and family history. Int J Cancer. 2016;138(3):576–83. DOI: 10.1002/ijc.29809
41. ESMO Interactive Guidelines. Metastatic colorectal cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. 2023. URL: http://interactiveguidelines.esmo.org/esmo-web-app/gl_toc/index.php?GL_id=74
42. Wills B., Gorse E., Lee V. Role of liquid biopsies in colorectal cancer. Curr Probl Cancer. 2018;42(6):593–600. DOI: 10.1016/j.currproblcancer.2018.08.004
43. Vacante M., Ciuni R., Basile F., Biondi A. The liquid biopsy in the management of colorectal cancer: An overview. Biomedicines. 2020;8(9):308. DOI: 10.3390/biomedicines8090308
44. Robertson D.J., Imperiale T.F. Stool testing for colorectal cancer screening. Gastroenterology. 2015;149(5):1286–93. DOI: 10.1053/j.gastro.2015.05.045
45. Binefa G., Rodríguez-Moranta F., Teule A., MedinaHayas M. Colorectal cancer: From prevention to personalized medicine. World J Gastroenterol. 2014;20(22):6786–808. DOI: 10.3748/wjg.v20.i22.6786
46. Marcuello M., Vymetalkova V., Neves R.P.L., DuranSanchon S., Vedeld H.M., Tham E., et al. Circulating biomarkers for early detection and clinical management of colorectal cancer. Mol Aspects Med. 2019;69:107–22. DOI: 10.1016/j.mam.2019.06.002
47. Ding Y., Li W., Wang K., Xu C., Hao M., Ding L. Perspectives of the application of liquid biopsy in colorectal cancer. Biomed Res Int. 2020;2020:6843180. DOI: 10.1155/2020/6843180
48. Dickinson B.T., Kisiel J., Ahlquist D.A., Grady W.M. Molecular markers for colorectal cancer screening. Gut. 2015;64(9):1485–94. DOI: 10.1136/gutjnl-2014-308075
49. Kościelniak-Merak B., Radosavljević B., Zając A., Tomasik P.J. Faecal occult blood point-of-care tests. J Gastrointest Cancer. 2018;49(4):402–5. DOI: 10.1007/s12029-018-0169-1
50. Rank K.M., Shaukat A. Stool based testing for colorectal cancer: An overview of available evidence. Curr Gastroenterol Rep. 2017;19(8):39. DOI: 10.1007/s11894-017-0579-4
51. Normanno N., Cervantes A., Ciardiello F., De Luca A., Pinto C. The liquid biopsy in the management of colorectal cancer patients: Current applications and future scenarios. Cancer Treat Rev. 2018;70:1–8. DOI: 10.1016/j.ctrv.2018.07.007
52. Viswanath B., Kim S., Lee K. Recent insights into nanotechnology development for detection and treatment of colorectal cancer. Int J Nanomedicine. 2016;11:2491–504. DOI: 10.2147/IJN.S108715
53. Brar B., Ranjan K., Patria A., Kumar R., Gosh M., Sihag S., et al. Nanotechnology in colorectal cancer for precision diagnosis and therapy. Front Nanotechnol. 2021;3:699266. DOI: 10.3389/fnano.2021.699266
54. Gogoi P., Kaur G., Singh N.K. Nanotechnology for colorectal cancer detection and treatment. World J Gastroenterol. 2022;28(46):6497–511. DOI: 10.3748/wjg.v28.i46.6497
55. Siddique S., Chow J.C.L. Gold nanoparticles for drug delivery and cancer therapy. Appl Sci. 2020;10(11):3824. DOI: 10.3390/app10113824
56. Rosado-de-Castro P.H., Morales M.D.P., PimentelCoelho P.M., Mendez-Otero R., Herranz F. Development and application of nanoparticles in biomedical imaging. Contrast Media Mol Imaging. 2018;2018:1403826. DOI: 10.1155/2018/1403826
57. Lécuyer T., Teston T., Ramirez-Garcia G., Maldiney T., Viana B., Seguin J., et al. Chemically engineered persistent luminescence nanoprobes for bioimaging. Theranostics. 2016;6(13):2488–524. DOI: 10.7150/thno.16589
58. Siddique S., Chow J.C.L. Application of nanomaterials in biomedical imaging and cancer therapy. Nanomaterials (Basel). 2020;10(9):1700. DOI: 10.3390/nano10091700
59. Younis N.K., Roumieh R., Bassil E.P., Ghoubaira J.A., Kobeissy F., Eid A.H. Nanoparticles: Attractive tools to treat colorectal cancer. Semin Cancer Biol. 2022;86(Pt 2):1–13. DOI: 10.1016/j.semcancer.2022.08.006
60. Carbary-Ganz J.L., Welge W.A., Barton J.K., Utzinger U. In vivo molecular imaging of colorectal cancer using quantum dots targeted to vascular endothelial growth factor receptor 2 and optical coherence tomography/laserinduced fluorescence dual-modality imaging. J Biomed Opt. 2015;20(9):096015. DOI: 10.1117/1.JBO.20.9.096015
61. Gu C., Guo C., Li Z., Wang M., Zhou N., He L., et al. Bimetallic ZrHf-based metal-organic framework embedded with carbon dots: Ultra-sensitive platform for early diagnosis of HER2 and HER2-overexpressed living cancer cells. Biosens Bioelectron. 2019;134:8–15. DOI: 10.1016/j.bios.2019.03.043
62. Kuo C.Y., Liu T.Y., Chan T.Y., Tsai S.C., Hardiansyah A., Huang L.Y., et al. Magnetically triggered nanovehicles for controlled drug release as a colorectal cancer therapy. Colloids Surf B Biointerfaces. 2016;140:567–73. DOI: 10.1016/j.colsurfb.2015.11.008
63. Esmaelbeygi E., Khoei S., Khoee S., Eynali S. Role of iron oxide core of polymeric nanoparticles in the thermosensitivity of colon cancer cell line HT-29. Int J Hyperthermia. 2015;31(5):489–97. DOI: 10.3109/02656736.2015.1035766
64. Akl M.A., Kartal-Hodzic A., Oksanen T., Ismael H.R., Afouna M.M., Yliperttula M., et al. Factorial design formulation optimization and in vitro characterization of curcumin-loaded PLGA nanoparticles for colon delivery. J Drug Deliv Sci Technol. 2016;32:10–20. DOI: 10.1016/j.jddst.2016.01.007
65. Tiwari A., Saraf S., Jain A., Panda P.K., Verma A., Jain S.K. Basics to advances in nanotherapy of colorectal cancer. Drug Deliv Transl Res. 2020;10(2):319–38. DOI: 10.1007/s13346-019-00680-9
66. González-Domínguez J.M., Grasa L., FrontiñánRubio J., Abás E., Domínguez-Alfaro A., Mesonero J.E., et al. Intrinsic and selective activity of functionalized carbon nanotube/nanocellulose platforms against colon cancer cells. Colloids Surf B Biointerfaces. 2022;212:112363. DOI: 10.1016/j.colsurfb.2022.112363
67. Abbasi E., Aval S.F., Akbarzadeh A., Milani M., Nasrabadi H.T., Joo S.W., et al. Dendrimers: Synthesis, applications, and properties. Nanoscale Res Lett. 2014;9(1):247. DOI: 10.1186/1556-276X-9-247
68. Xie J., Gao Y., Zhao R., Sinko P.J., Gu S., Wang J., et al. Ex vivo and in vivo capture and deactivation of circulating tumor cells by dual-antibody-coated nanomaterials. J Control Release. 2015;209:159–69. DOI: 10.1016/j.jconrel.2015.04.036
69. Shazleen Ibrahim I., Starlin Chellathurai M., Mahmood S., Hakim Azmi A., Harun N., Ulul Ilmie Ahmad Nazri M., et al. Engineered liposomes mediated approach for targeted colorectal cancer drug Delivery: A review. Int J Pharm. 2024;651:123735. DOI: 10.1016/j.ijpharm.2023.123735
70. Patil Y.P., Jadhav S. Novel methods for liposome preparation. Chem Phys Lipids. 2014;177:8–18. DOI: 10.1016/j.chemphyslip.2013.10.011
71. Meng J., Wang Z.G., Zhao X., Wang Y., Chen D.Y., Liu D.L., et al. Silica nanoparticle design for colorectal cancer treatment: Recent progress and clinical potential. World J Clin Oncol. 2024;15(6):667–73. DOI: 10.5306/wjco.v15.i6.667
72. Zhao X., Pan J., Li W., Yang W., Qin L., Pan Y. Gold nanoparticles enhance cisplatin delivery and potentiate chemotherapy by decompressing colorectal cancer vessels. Int J Nanomedicine. 2018;13:6207–21. DOI: 10.2147/IJN.S176928
73. Linton S.S., Sherwood S.G., Drews K.C., Kester M. Targeting cancer cells in the tumor microenvironment: opportunities and challenges in combinatorial nanomedicine. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2016;8(2):208–22. DOI: 10.1002/wnan.1358
74. Anitha A., Maya S., Sivaram A.J., Mony U., Jayakumar R. Combinatorial nanomedicines for colon cancer therapy. Wiley Interdiscip Rev Nanomed. Nanobiotechnol. 2016;8(1):151–9. DOI: 10.1002/wnan.1353
Review
For citations:
Rao Sh.A., Varenya V., Samanvitha H.S., Prasad S.N., Paari K.A., George J.A. Deciphering Colorectal Cancer Development: From Genomic and Metabolic Perspectives to Innovative Diagnostic Approaches and Nanotechnology-Based Management Strategies. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2025;35(3):7-20. https://doi.org/10.22416/1382-4376-2025-35-3-7-20