Surgery and OncologySurgery and OncologyХирургия и онкология2949-5857Publishing House ABV Press65710.17650/2949-5857-2023-13-4-54-61LITERATURE REVIEWОБЗОР ЛИТЕРАТУРЫMolecular mechanisms of colorectal cancer formation and their significance (literature review)Молекулярные механизмы формирования колоректального рака и их значение (обзор литературы)NavruzovS. N.НаврузовС. Н.
Uzbekistan

Sarimbek Navruzovich Navruzov

3 Karakamysh St., Tashkent 3100057

Саримбек Наврузович Наврузов

100057 Ташкент, ул. Каракамыш, 3

sarinbekn@list.ruNavruzovB. S.НаврузовБ. С.
Uzbekistan

2 Farobi St., Tashkent 100109

100109 Ташкент, ул. Фароби, 2

RakhmonovS. T.РахмоновС. Т.
Uzbekistan

3 Karakamysh St., Tashkent 3100057

100057 Ташкент, ул. Каракамыш, 3

KhakimovA. M.ХакимовА. М.
Uzbekistan

3 Karakamysh St., Tashkent 3100057

100057 Ташкент, ул. Каракамыш, 3

KulmievE. E.КулмиевЭ. Э.
Uzbekistan

3 Karakamysh St., Tashkent 3100057

100057 Ташкент, ул. Каракамыш, 3

ChorievKh. Kh.ЧориевХ. Х.
Uzbekistan

3 Karakamysh St., Tashkent 3100057

100057 Ташкент, ул. Каракамыш, 3

AlievaD. A.АлиеваД. А.
Uzbekistan

18 Amir Timur St., Samarkand 140100

140100 Самарканд, ул. Амира Тимура, 18

Surgical Clinic “Yangi Hayot”Хирургическая клиника “Yangi Hayot”Tashkent Medical AcademyТашкентская медицинская академияSamarkand State Medical UniversityСамаркандский государственный медицинский университет0801202413454610401202404012024Copyright ©; 2024, Navruzov S.N., Navruzov B.S., Rakhmonov S.T., Khakimov A.M., Kulmiev E.E., Choriev K.K., Alieva D.A.Copyright ©; 2024, Наврузов С.Н., Наврузов Б.С., Рахмонов С.Т., Хакимов А.М., Кулмиев Э.Э., Чориев Х.Х., Алиева Д.А.2024Navruzov S.N., Navruzov B.S., Rakhmonov S.T., Khakimov A.M., Kulmiev E.E., Choriev K.K., Alieva D.A.Наврузов С.Н., Наврузов Б.С., Рахмонов С.Т., Хакимов А.М., Кулмиев Э.Э., Чориев Х.Х., Алиева Д.А.https://creativecommons.org/licenses/by/4.0https://onco-surgery.info/jour/article/view/657

Colorectal cancer remains an urgent problem of oncological proctology and requires active efforts to study risk factors, mechanisms for the formulation and search for genetic components that play a key role in determining the prognosis of the disease. This article analyzes the molecular mechanisms of colorectal cancer formation, factors of transformation of adenoma formation, pathogenesis and molecular nature of CRC. Subtypes based on transcription signatures allow for better refinement and provide insight into the development of subtype-specific treatment methods, which, in turn, can contribute to more effective treatment of this disease.

Колоректальный рак остается актуальной проблемой онкоколопроктологии и требует активных усилий по изучению факторов риска, механизмов формирования и поиска генетических составляющих, играющих ключевую роль в определении прогноза заболевания. В данной статье проанализированы молекулярные механизмы формирования колоректального рака, факторы трансформации формирования аденомы, патогенез и молекулярная природа колоректального рака. Классификация, основанная на транскрипционных сигнатурах, позволяет лучше уточнять подтип и дает представление о разработке методов лечения, специфичных для подтипа, что, в свою очередь, может способствовать более эффективному лечению этого заболевания.

colorectal cancergenetic subtypesadenoma formationcolon cancercarcinomasколоректальный ракгенетические подтипыформирование аденомырак толстой кишкикарциномыStarostin R.A., Gataullin B.I., Valitov B.R. et al. Colorectal cancer: epidemiology and risk factors. Povolzhskij onkologicheskij vestnik = Oncology bulletin of the Volga region 2021;12(4):52–9. (In Russ.).Старостин Р.А., Гатауллин Б.И., Валитов Б.Р. и др. Колоректальный рак: эпидемиология и факторы риска. Поволжский онкологический вестник 2021;12(4):52–9.Ageikina N.V., Duvansky V.A., Knyazev M.V. et al. An alternative way of developing colorectal cancer. Histogenetic and molecular features of tooth lesions. Eksperimental’naya i klinicheskaya gastroenterologiya = Experimental and clinical gastroenterology journal 2014;(7):4–12. (in Russ.).Агейкина Н.В., Дуванский В.А., Князев М.В. и др. Альтернативный путь развития колоректального рака. Гистогенетические и молекулярные особенности зубчатых поражений. Экспериментальная и клиническая гастроэнтерология 2014;(7):4–12.Maximova P.E., Golubinskaya E.P., Seferov B.D. et al. Colorectal cancer: epidemiology, carcinogenesis, molecular genetic and cellular mechanisms of resistance to therapy (analytical review). Koloproktologiya = Koloproktologia 2023;22(2):160–71. (in Russ.). Https://doi.org/10.33878/2073-7556-2023-22-2-160-171Максимова П.Е., Голубинская Е.П., Сеферов Б.Д. и др. Колоректальный рак: эпидемиология, канцерогенез, молекулярно-генетические и клеточные механизмы резистентности к терапии (аналитический обзор). Колопроктология 2023;22(2):160–71. Https://doi.org/10.33878/2073-7556-2023-22-2-160-171World Health Organization. Cancer. Newsletter. 2021. Https://www.who.int/ru/news-room/fact-sheets/detail/cancer/Demidova D.A. Colorectal cancer. Study guide. Yekaterinburg: UGSU, 2021. 60 p. (in Russ).Демидова Д.А. Колоректальный рак. Учеб. пособие. Екатеринбург: УГМУ, 2021. 60 с.Cheng T.H., Gorman M., Martin L. et al. Common colorectal cancer risk alleles contribute to the multiple colorectal adenoma phenotype, but do not influence colonic polyposis in FAP. Eur J Hum Genet 2015;23(2):260–3. DOI: 10.1038/ejhg.2014.74An N., Zhao C., Yu Z. et al. Identification of prognostic genes in colorectal cancer through transcription profiling of multi-stage carcinogenesis. Oncol Lett 2019;17(1):432–41. DOI: 10.3892/ol.2018.9632Tosi F., Magni E., Amatu A. et al. Effect of KRAS and BRAF mutations on survival of metastatic colorectal cancer after liver resection: a systematic review and meta-analysis. Clin Colorectal Cancer 2017;16(3):e153–63. DOI: 10.1016/j.clcc.2017.01.004Mozerov S.A., Komin Yu.A., Novikov N.Yu. et al. Tumor response to neoadjuvant therapy in colorectal cancer. Zhurnal nauchnyh statej “Zdorov’e i obrazovanie v millennium” = The journal of scientific articles health and education millennium 2018:20(4):99–108. (in Russ.).Мозеров С.А., Комин Ю.А., Новиков Н.Ю. и др. Опухолевый ответ на неоадъювантную терапию при колоректальном раке. Журнал научных статей «Здоровье и образование в XXI веке» 2018:20(4):99–108.Kit O.I., Jenkova E.A., Mirzoyan E.A. et al. Molecular genetic classification of subtypes of colorectal cancer: the current state of the problem. Yuzhno-Rossijskij onkologicheskij zhurnal = South Russian journal of cancer 2021;2(2):50–6. (in Russ.). DOI: 10.37748/2686-9039-2021-2-2-6Кит О.И., Дженкова Е.А., Мирзоян Э.А. и др. Молекулярногенетическая классификация подтипов колоректального рака: современное состояние проблемы. Южно-Российский онкологический журнал 2021;2(2):50–6. DOI: 10.37748/2686-9039-2021-2-2-6Roth A.D., Tejpar S., Delorenzi M. et al. Prognostic role of KRAS and BRAF in stage II and III resected colon cancer: Results of the translational study on the PETACC-3, EORTC 40993, SAKK 60-00 trial. J Clin Oncol 2019;28(3):466–74. DOI: 10.1200/JCO.2009.23.3452Aoki K., Taketo M.M. Adenomatous polyposis coli (APC): A multi-functional tumor suppressor gene. J Cell Sci 2007; 120(Pt 19):3327–35. DOI: 10.1242/jcs.03485Lenz H.-J.J., Van Cutsem E., Limon M.L. et al. Durable clinical benefit with nivolumab (NIVO) plus low-dose ipilimumab (IPI) as first-line therapy in microsatellite instability-high/mismatch repair deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC). Ann Oncol 2018(supl 8);29:714. DOI: https://doi.org/10.1093/annonc/mdy424.019Bogaert J., Prenen H. Molecular genetics of colorectal cancer. Ann Gastroenterol 2014;27(1):9–14.Le Marchand L., Wilkens L.R., Hankin J.H. et al. A case-control study of diet and colorectal cancer in a multiethnic population in Hawaii (United States): Lipids and foods of animal origin. Cancer Causes Control 2017;8(4):637–48. DOI: 10.1023/a:1018406716115Wirtzfeld D.A., Petrelli N.J., Rodriguez-Bigas M.A. Hamartomatous polyposis syndromes: Molecular genetics, neoplastic risk, and surveillance recommendations. Ann. Surg Oncol 2021;8(4):319–27. DOI: 10.1007/s10434-001-0319-7Xie J., Itzkowitz S.H. Cancer in inflammatory bowel disease. World J Gastroenterol 2018;14(3):378–89. DOI: 10.3748/wjg.14.378Fearon E.R., Vogelstein B. A genetic model for colorectal tumorigenesis. Cell 1990;61(5):759–67. DOI: 10.1016/0092-8674(90)90186-iGrady W.M., Markowitz S.D. Genetic and epigenetic alterations in colon cancer. Ann Rev Genom Hum Genet 2002;3:101–28. DOI: 10.1146/annurev.genom.3.022502.103043Leary R.J., Lin J.C., Cummins J. et al. Integrated analysis of homozygous deletions, focal amplifications, and sequence alterations in breast and colorectal cancers. Proc Natl Acad Sci USA 2008;105(42):16224–9. DOI: 10.1073/pnas.0808041105Lin J.K., Chang S.C., Yang Y.C., Li A.F. Loss of heterozygosity and DNA aneuploidy in colorectal adenocarcinoma. Ann Surg Oncol 2003;10(9):1086–94. DOI: 10.1245/aso.2003.12.014Van Geel R., Tabernero J., Elez E. et al. A Phase Ib dose-escalation study of encorafenib and cetuximab with or without alpelisib in metastatic BRAF-mutant colorectal cancer. Cancer Discov 2017;7(6):610–9. DOI: 10.1158/2159-8290.CD-16-0795Wei W., Chua M.S., Grepper S., So S.K. Soluble Frizzled-7 receptor inhibits Wnt signaling and sensitizes hepatocellular carcinoma cells towards doxorubicin. Mol Cancer 2011;10:16. DOI: 10.1186/1476-4598-10-16Kosmidou V., Oikonomou E., Vlassi M. et al. Tumor heterogeneity revealed by KRAS, BRAF, and PIK3CA pyrosequencing: KRAS and PIK3CA intratumor mutation profile differences and their therapeutic implications. Hum Mutat 2014;35(3):329–40. DOI: 10.1002/humu.22496Hanon B.M., Al-Mohaimen Mohammad N.A., Mahmood A.S. CpG island methylator phenotype (CIMP) correlation with clinical and morphological feature of colorectal cancer in iraq patients. Pan Arab J Oncol 2015;8:6–13.Luebeck E.G., Moolgavkar S.H. Multistage carcinogenesis and the incidence of colorectal cancer. Proc Natl Acad Sci USA 2002;99: 15095. DOI: 10.1073/pnas.222118199Corcoran R.B., André T., Atreya C.E. et al. Combined BRAF, EGFR, and MEK inhibition in patients with BRAF (V600E)-mutant colorectal cancer. Cancer Discov 2018;8(4):428–443. DOI: 10.1158/2159-8290.CD-17-1226Tsang A.H., Cheng K.H., Wong A.S. et al. Current and future molecular diagnostics in colorectal cancer and colorectal adenoma. World J Gastroenterol 2014;20(14):3847–57. DOI: 10.3748/wjg.v20.i14.3847Markowitz S., Wang J., Myeroff L. et al. Inactivation of the type II TGF-beta receptor in colon cancer cells with microsatellite instability. Science 1995;268(5215):1336–8. DOI: 10.1126/science.7761852Samuels Y., Wang Z., Bardelli A. et al. High frequency of mutations of the PIK3CA gene in human cancers. Science 2004;304(5670):554. DOI: 10.1126/science.1096502Thiagalingam S., Lengauer C., Leach F.S. et al. Evaluation of candidate tumour suppressor genes on chromosome 18 in colorectal cancers. Nat Genet 1996;13(3):343–6. DOI: 10.1038/ng0796-343Puccini A., Berger M.D., Naseem M. et al. Colorectal cancer: Epigenetic alterations and their clinical implications. BBA Rev Cancer 2017;1868(2):439–48. DOI: 10.1016/j.bbcan.2017.09.003Manes M., Garcia-Gomes M.S.A., Sandini T.M. et al. Behavioral and neurochemical characterization of the mlh mutant mice lacking otoconia. Behav Brain Res 2019;359:958–66. DOI: 10.1016/j.bbr.2018.06.012Christie M., Jorissen R.N., Mouradov D. et al. Different APC genotypes in proximal and distal sporadic colorectal cancers suggest distinct WNT/β-catenin signalling thresholds for tumourigenesis. Oncogene 2013;32(39):4675–82. DOI: 10.1038/onc.2012.486Pronobis M.I., Rusan N.M., Peifer M. A novel GSK3-regulated APC: Axin interaction regulates Wnt signaling by driving a catalytic cycle of efficient βcatenin destruction. Elife 2015;4:e08022. DOI: 10.7554/eLife.08022He L., Lu N., Dai Q. et al. Wogonin induced G1 cell cycle arrest by regulating Wnt/β-catenin signaling pathway and inactivating CDK8 in human colorectal cancer carcinoma cells. Toxicology 2013;312:36–47. DOI: 10.1016/j.tox.2013.07.013He T.C., Sparks A.B., Rago C. et al. Identification of c-MYC as a target of the APC pathway. Science 1998;281(5382):1509–12. DOI: 10.1126/science.281.5382.1509Manthravadi S., Sun W., Saeed A. Prognostic impact of BRAF V600E mutation in patients with non-metastatic colorectal cancer with microsatellite instability: A systematic review and meta-analysis. J Clin Oncol 2018;36(15 suppl):3597. DOI: 10.1200/JCO.2018.36.15_suppl.3597Frouws M.A., Reimers M.S., Swets M. et al. The influence of BRAF and KRAS mutation status on the association between aspirin use and survival after colon cancer diagnosis. PLoS One 2017;12(1):e0170775. DOI: 10.1371/journal.pone.0170775Wang Y., Liu D., Jin X. et al. Genome-wide characterization of aberrant DNA methylation patterns and the potential clinical implications in patients with endometrial cancer. Pathol Res Pract 2019;215(1):137–43. DOI: 10.1016/j.prp.2018.11.002Schwarzenbach H. Loss of heterozygosity. Eds. Maloy S., Hughes K. Brenner’s Encyclopedia of Genetics. 2nd ed. San Diego, CA, USA: Academic Press, 2013. Pp. 271–3.Boland C.R., Goel A. Microsatellite instability in colorectal cancer. Gastroenterology 2010;138(6):2087. DOI: 10.1053/j.gastro.2009.12.064Vaqué J.P., Martínez N., Varela I. et al. Colorectal adenomas contain multiple somatic mutations that do not coincide with synchronous adenocarcinoma specimens. PLoS One 2015;10(3): 1–12. DOI: 10.1371/journal.pone.0119946Tabernero J., Geel R.V., Guren T.K. et al. Phase 2 results: Encorafenib (ENCO) and cetuximab (CETUX) with or without alpelisib (ALP) in patients with advanced BRAF-mutant colorectal cancer (BRAFm CRC). J Clin Oncol 2016;34:3544.Xie Y.H., Chen Y.X., Fang J.Y. Comprehensive review of targeted therapy for colorectal cancer. Signal Transduct Target Ther 2020;5(1):22. DOI: 10.1038/s41392-020-0116-zShimada Y., Tajima Y., Nagahashi M. et al. Clinical significance of BRAF Non-V600E mutations in colorectal cancer: a retrospective study of two institutions. J Surg Res 2018;232:72–81. DOI: 10.1016/j.jss.2018.06.020Suzuki H., Yamamoto E., Maruyama R. et al. Biological significance of the CpG island methylator phenotype. Biochem Biophys Res Commun 2014;455(1–2):35–42. DOI: 10.1016/j.bbrc.2014.07.007