medalphabetМедицинский алфавитMedical alphabet2078-56312949-2807ООО «Альфмед»10.33667/2078-5631-2024-7-46-54medalphabet-3688Research ArticleДИАГНОСТИКА И ОНКОТЕРАПИЯDIAGNOSTICS AND ONCOTHERAPYАнализ циркулирующей опухолевой ДНК и новые возможности использования анти-EGFR моноклональных антител у пациентов с метастатическим колоректальным ракомCirculating tumour DNA analysis and new uses of anti-EGFR monoclonal antibodies in patients with metastatic colorectal cancerРубанМ. С.RubanM. S.

Рубан Максим Сергеевич - врач-аспирант отделения химиотерапии отдела лекарственного лечения опухолей

 Author ID: 1170985

Москва

Ruban Maxim S. - postgraduate student at Dept of Chemotherapy, Systemic Treatment of Solid Tumors Dept

Author ID: 1170985

Moscow

ruban.m.s@yandex.ruhttps://orcid.org/0000-0003-4879-2687БолотинаЛ. В.BolotinaL. V.

Болотина Лариса Владимировна - д.м.н., зав. отделением химиотерапии отдела лекарственного лечения опухолей

AuthorID: 594953

Москва

Bolotina Larisa V. - DM Sci (habil.), head of the chemotherapy Dept, Systemic Treatment of Solid Tumors Dept.

AuthorID: 594953

Moscow

lbolotina@yandex.ruhttps://orcid.org/0000-0003-3196-1368КарагодинаЮ. Б.KaragodinaYu. B.

Карагодина Юлия Борисовна - научный сотрудник отдела лекарственного лечения опухолей

AuthorID: 1170902

Москва

Karagodina Yulia B. - researcher at Systemic Treatment of Solid Tumors Dept

 AuthorID: 1170902

Moscow

yuliaborisovnakaragodina@gmail.comhttps://orcid.org/0000-0002-3371-7548ДешкинаТ. И.DeshkinaT. I.

Дешкина Татьяна Игоревна - к.м.н., старший научный сотрудник отдела лекарственного лечения опухолей

AuthorID: 878173

 Москва

Deshkina Tatyana I. - PhD Med, senior researcher at Systemic Treatment of Solid Tumors Dept 

 AuthorID: 878173

Moscow

rew9@yandex.ruhttps://orcid.org/0000-0003-0092-0459КорниецкаяА. Л.KornietskayaA. L.

Корниецкая Анна Леонидовна - к.м.н., ведущий научный сотрудник отдела лекарственного лечения опухолей

 AuthorID: 951395

Москва

Kornietskaya Anna L. - PhD Med, leading researcher at Systemic Treatment of Solid Tumors Dept

AuthorID: 951395

Moscow

kornietskaya@mail.ruhttps://orcid.org/0000-0003-4927-5585ФеденкоА. А.FedenkoA. A.

Феденко Александр Александрович - д.м.н., профессор, рук. отдела лекарственного лечения опухолей

AuthorID: 823233

Москва

Fedenko Alexander A. - DM Sci (habil.), professor, head of Systemic Treatment of Solid Tumors Dept

AuthorID: 823233

Moscow

fedenko@eesg.ruМосковский научно-исследовательский онкологический институт имени П.А. Герцена – филиал ФГБУ «Национальный медицинский исследовательский центр радиологии»РоссияMoscow Research Institute n.a. P.A. Herzen – a Branch of the National Medical Research Centre of RadiologyRussian FederationМосковский научно-исследовательский онкологический институт имени П.А. Герцена – филиал ФГБУ «Национальный медицинский исследовательский центр радиологии»РоссияMoscow Research Institute n.a. P.A. Herzen – a Branch of the National Medical Research Centre of RadiologyRussian Federation20241005202407«Диагностика и онкотерапия» (1)4654Copyright © Рубан М.С., Болотина Л.В., Карагодина Ю.Б., Дешкина Т.И., Корниецкая А.Л., Феденко А.А., 20242024Рубан М.С., Болотина Л.В., Карагодина Ю.Б., Дешкина Т.И., Корниецкая А.Л., Феденко А.А.Ruban M.S., Bolotina L.V., Karagodina Y.B., Deshkina T.I., Kornietskaya A.L., Fedenko A.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.med-alphabet.com/jour/article/view/3688

В настоящее время исследование биоптата опухолевой ткани с целью определения альтераций в генах RAS/BRAF, оценки статуса микросателлитной нестабильности, а также определения амплификации/гиперэкспрессии гена HER‑2/neu является золотым стандартом диагностики и позволяет осуществить выбор оптимальной молекулярно-направленной терапии при рассмотрении стратегий лечения пациентов с метастатическим колоректальным раком. Однако биопсия не позволяет в полной мере отразить существующую внутриопухолевую гетерогенность и клональную эволюцию опухолевых клеток, что, зачастую, может быть причиной терапевтических неудач. В последние годы жидкостная биопсия привлекает все большее внимание как дополнительный и потенциально альтернативный неинвазивный инструмент молекулярного профилирования опухоли. Оценка циркулирующей опухолевой ДНК позволяет отслеживать изменения генетического статуса опухоли, а также динамически измерять «бремя» болезни в режиме реального времени. Благодаря развитию технологий жидкостной биопсии появились новые многообещающие стратегии ведения пациентов с метастатическим колоректальным раком на поздних линиях терапии. Стандартный лекарственный арсенал у данной группы больных ограничен или повторным назначением ранее эффективной терапии или регорафенибом и комбинацией трифлуридин/типирацила с бевацизумабом, которые характеризуются ограниченной клинической активностью. Однако, благодаря открытию феномена NeoRAS wild-type истратегии rechallenge анти-EGFR моноклональных антител, основанных на изучении клональной селекции и эволюции опухолевых клеток, назначение ингибиторов эпидермального фактора роста в молекулярно-отобранной посредством жидкостной биопсии популяции сопровождается хорошей переносимостью и эффективностью. В настоящий момент продолжаются многочисленные клинические исследования, направленные на дальнейшее понимание механизмов резистентности опухоли и разработку новых научно обоснованных лечебных подходов с целью реализации концепции персонализированной медицины.

Currently, tumour tissue biopsy to determine RAS/BRAF gene alterations, assess microsatellite instability status, and determine HER‑2/neu gene amplification/hyperexpression is the gold standard of diagnosis and allows the selection of optimal molecularly targeted therapy when considering treatment strategies for patients with metastatic colorectal cancer. However, biopsy does not fully reflect the existing intratumoural heterogeneity and clonal evolution of tumour cells, which can often be the cause of therapeutic failures. In recent years, liquid biopsy has attracted increasing attention as an additional and potentially alternative non-invasive tool for molecular tumour profiling. Assessment of circulating tumour DNA allows changes in the genetic status of the tumour to be monitored and the «burden» of disease to be measured dynamically in real time. Advances in liquid biopsy technology have led to promising new strategies for the management of patients with metastatic colorectal cancer in late-line therapy. The standard drug arsenal in this group of patients is limited to either repeat administration of previously effective therapy or regorafenib and the combination of trifluridine/tipiracil with bevacizumab, which are characterized by limited clinical activity. However, thanks to the discovery of the NeoRAS wild-type phenomenon and the rechallenge strategy of anti-EGFR monoclonal antibodies based on the study of clonal selection and evolution of tumour cells, the administration of epidermal growth factor inhibitors in a molecularly selected by liquid biopsy population is accompanied by good tolerability and efficacy. Numerous clinical studies are ongoing to further understand the mechanisms of tumour resistance and to develop new evidence-based treatment approaches in order to realise the concept of personalised medicine.

колоректальный ракжидкостная биопсияциркулирующая опухолевая ДНКтаргетная терапиярезистентностьcolorectal cancerliquid biopsycirculating tumour DNAtargeted therapyresistanceReferencesSung H. et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries // CA. Cancer J. Clin. 2021. Vol. 71, № 3. P. 209–249.Sung H. et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries // CA. Cancer J. Clin. 2021. Vol. 71, № 3. P. 209–249.Global Burden of Disease 2019 Cancer Collaboration. Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life Years for 29 Cancer Groups From 2010 to 2019: A Systematic Analysis for the Global Burden of Disease Study 2019 // JAMA Oncol. 2022. Vol. 8, № 3. P. 420–444.Global Burden of Disease 2019 Cancer Collaboration. Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life Years for 29 Cancer Groups From 2010 to 2019: A Systematic Analysis for the Global Burden of Disease Study 2019 // JAMA Oncol. 2022. Vol. 8, № 3. P. 420–444.B V. et al. Genetic alterations during colorectal-tumor development // N. Engl. J. Med. N Engl J Med, 1988. Vol. 319, № 9.B V. et al. Genetic alterations during colorectal-tumor development // N. Engl. J. Med. N Engl J Med, 1988. Vol. 319, № 9.Jy B., A T., Jp M. Exploring and modelling colon cancer inter-tumour heterogeneity: opportunities and challenges // Oncogenesis. Oncogenesis, 2020. Vol. 9, № 7.Jy B., A T., Jp M. Exploring and modelling colon cancer inter-tumour heterogeneity: opportunities and challenges // Oncogenesis. Oncogenesis, 2020. Vol. 9, № 7.F D.N. et al. Precision oncology in metastatic colorectal cancer – from biology to medicine // Nat. Rev. Clin. Oncol. Nat Rev Clin Oncol, 2021. Vol. 18, № 8.F D.N. et al. Precision oncology in metastatic colorectal cancer – from biology to medicine // Nat. Rev. Clin. Oncol. Nat Rev Clin Oncol, 2021. Vol. 18, № 8.Van Cutsem E. et al. ESMO consensus guidelines for the management of patients with metastatic colorectal cancer // Ann. Oncol. Off. J. Eur. Soc. Med. Oncol. 2016. Vol. 27, № 8. P. 1386–1422.Van Cutsem E. et al. ESMO consensus guidelines for the management of patients with metastatic colorectal cancer // Ann. Oncol. Off. J. Eur. Soc. Med. Oncol. 2016. Vol. 27, № 8. P. 1386–1422.Martini G. et al. Resistance to anti-epidermal growth factor receptor in metastatic colorectal cancer: What does still need to be addressed? // Cancer Treat. Rev. 2020. Vol. 86. P. 102023.Martini G. et al. Resistance to anti-epidermal growth factor receptor in metastatic colorectal cancer: What does still need to be addressed? // Cancer Treat. Rev. 2020. Vol. 86. P. 102023.Parseghian C.M. et al. Mechanisms of Innate and Acquired Resistance to Anti-EGFR Therapy: A Review of Current Knowledge with a Focus on Rechallenge Therapies // Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res. 2019. Vol. 25, № 23. P. 6899–6908.Parseghian C.M. et al. Mechanisms of Innate and Acquired Resistance to Anti-EGFR Therapy: A Review of Current Knowledge with a Focus on Rechallenge Therapies // Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res. 2019. Vol. 25, № 23. P. 6899–6908.Van Cutsem E. et al. Fluorouracil, leucovorin, and irinotecan plus cetuximab treatment and RAS mutations in colorectal cancer // J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol. 2015. Vol. 33, № 7. P. 692–700.Van Cutsem E. et al. Fluorouracil, leucovorin, and irinotecan plus cetuximab treatment and RAS mutations in colorectal cancer // J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol. 2015. Vol. 33, № 7. P. 692–700.Ciardiello F. et al. Clinical management of metastatic colorectal cancer in the era of precision medicine // CA. Cancer J. Clin. 2022. Vol. 72, № 4. P. 372–401.Ciardiello F. et al. Clinical management of metastatic colorectal cancer in the era of precision medicine // CA. Cancer J. Clin. 2022. Vol. 72, № 4. P. 372–401.Arnold D. et al. Prognostic and predictive value of primary tumour side in patients with RAS wild-type metastatic colorectal cancer treated with chemotherapy and EGFR directed antibodies in six randomized trials // Ann. Oncol. Off. J. Eur. Soc. Med. Oncol. 2017. Vol. 28, № 8. P. 1713–1729.Arnold D. et al. Prognostic and predictive value of primary tumour side in patients with RAS wild-type metastatic colorectal cancer treated with chemotherapy and EGFR directed antibodies in six randomized trials // Ann. Oncol. Off. J. Eur. Soc. Med. Oncol. 2017. Vol. 28, № 8. P. 1713–1729.Wang Z.-X. et al. Chemotherapy With or Without Anti-EGFR Agents in Left- and Right-Sided Metastatic Colorectal Cancer: An Updated Meta-Analysis // J. Natl. Compr. Canc. Netw. National Comprehensive Cancer Network, 2019. Vol. 17, № 7. P. 805–811.Wang Z.-X. et al. Chemotherapy With or Without Anti-EGFR Agents in Left- and Right-Sided Metastatic Colorectal Cancer: An Updated Meta-Analysis // J. Natl. Compr. Canc. Netw. National Comprehensive Cancer Network, 2019. Vol. 17, № 7. P. 805–811.Sunakawa Y. et al. No benefit from the addition of anti-EGFR antibody in all right-sided metastatic colorectal cancer? // Ann. Oncol. Elsevier, 2017. Vol. 28, № 8. P. 2030–2031.Sunakawa Y. et al. No benefit from the addition of anti-EGFR antibody in all right-sided metastatic colorectal cancer? // Ann. Oncol. Elsevier, 2017. Vol. 28, № 8. P. 2030–2031.ten Hoorn S. et al. Molecular subtype-specific efficacy of anti-EGFR therapy in colorectal cancer is dependent on the chemotherapy backbone: 8 // Br.J. Cancer. Nature Publishing Group, 2021. Vol. 125, № 8. P. 1080–1088.ten Hoorn S. et al. Molecular subtype-specific efficacy of anti-EGFR therapy in colorectal cancer is dependent on the chemotherapy backbone: 8 // Br.J. Cancer. Nature Publishing Group, 2021. Vol. 125, № 8. P. 1080–1088.Guinney J. et al. The consensus molecular subtypes of colorectal cancer: 11 // Nat. Med. Nature Publishing Group, 2015. Vol. 21, № 11. P. 1350–1356.Guinney J. et al. The consensus molecular subtypes of colorectal cancer: 11 // Nat. Med. Nature Publishing Group, 2015. Vol. 21, № 11. P. 1350–1356.Benson A.B. et al. Rectal Cancer, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology // J. Natl. Compr. Canc. Netw. National Comprehensive Cancer Network, 2022. Vol. 20, № 10. P. 1139–1167.Benson A.B. et al. Rectal Cancer, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology // J. Natl. Compr. Canc. Netw. National Comprehensive Cancer Network, 2022. Vol. 20, № 10. P. 1139–1167.Benson A.B. et al. Colon Cancer, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology // J. Natl. Compr. Canc. Netw. National Comprehensive Cancer Network, 2021. Vol. 19, № 3. P. 329–359.Benson A.B. et al. Colon Cancer, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology // J. Natl. Compr. Canc. Netw. National Comprehensive Cancer Network, 2021. Vol. 19, № 3. P. 329–359.R G. et al. Second-line angiogenesis inhibition in metastatic colorectal cancer patients: Straightforward or overcrowded? // Crit. Rev. Oncol. Hematol. Crit Rev Oncol Hematol, 2016. Vol. 100.R G. et al. Second-line angiogenesis inhibition in metastatic colorectal cancer patients: Straightforward or overcrowded? // Crit. Rev. Oncol. Hematol. Crit Rev Oncol Hematol, 2016. Vol. 100.Федянин М.Ю. et al. Практические рекомендации по лекарственному лечению рака ободочной кишки, ректосигмоидного соединения и прямой кишки: 3s2–1 // Злокачественные Опухоли. 2022. Vol. 12, № 3s2–1. P. 401–454.Fedyanin M. Yu. et al. Practical recommendations for drug treatment of cancer of the colon, rectosigmoid junction and rectum: 3s2–1 // Malignant Tumors. 2022. Vol. 12, No. 3s2–1. P. 401–454.Misale S. et al. Resistance to anti-EGFR therapy in colorectal cancer: from heterogeneity to convergent evolution // Cancer Discov. 2014. Vol. 4, № 11. P. 1269–1280.Misale S. et al. Resistance to anti-EGFR therapy in colorectal cancer: from heterogeneity to convergent evolution // Cancer Discov. 2014. Vol. 4, № 11. P. 1269–1280.Santini D. et al. Cetuximab rechallenge in metastatic colorectal cancer patients: how to come away from acquired resistance? // Ann. Oncol. 2012. Vol. 23, № 9. P. 2313–2318.Santini D. et al. Cetuximab rechallenge in metastatic colorectal cancer patients: how to come away from acquired resistance? // Ann. Oncol. 2012. Vol. 23, № 9. P. 2313–2318.Cremolini C. et al. Rechallenge for Patients With RAS and BRAF Wild-Type Metastatic Colorectal Cancer With Acquired Resistance to First-line Cetuximab and Irinotecan: A Phase 2 Single-Arm Clinical Trial // JAMA Oncol. 2019. Vol. 5, № 3. P. 343–350.Cremolini C. et al. Rechallenge for Patients With RAS and BRAF Wild-Type Metastatic Colorectal Cancer With Acquired Resistance to First-line Cetuximab and Irinotecan: A Phase 2 Single-Arm Clinical Trial // JAMA Oncol. 2019. Vol. 5, № 3. P. 343–350.Sunakawa Y. et al. RAS Mutations in Circulating Tumor DNA and Clinical Outcomes of Rechallenge Treatment With Anti-EGFR Antibodies in Patients With Metastatic Colorectal Cancer // JCO Precis. Oncol. Wolters Kluwer, 2020. № 4. P. 898–911.Sunakawa Y. et al. RAS Mutations in Circulating Tumor DNA and Clinical Outcomes of Rechallenge Treatment With Anti-EGFR Antibodies in Patients With Metastatic Colorectal Cancer // JCO Precis. Oncol. Wolters Kluwer, 2020. № 4. P. 898–911.Parseghian C.M. et al. Anti-EGFR-resistant clones decay exponentially after progression: implications for anti-EGFR re-challenge // Ann. Oncol. 2019. Vol. 30, № 2. P. 243–249.Parseghian C.M. et al. Anti-EGFR-resistant clones decay exponentially after progression: implications for anti-EGFR re-challenge // Ann. Oncol. 2019. Vol. 30, № 2. P. 243–249.Osumi H. et al. NeoRAS wild-type in metastatic colorectal cancer: Myth or truth?—Case series and review of the literature // Eur. J. Cancer. Elsevier, 2021. Vol. 153. P. 86–95.Osumi H. et al. NeoRAS wild-type in metastatic colorectal cancer: Myth or truth?—Case series and review of the literature // Eur. J. Cancer. Elsevier, 2021. Vol. 153. P. 86–95.Simanshu D.K., Nissley D.V., McCormick F. RAS Proteins and Their Regulators in Human Disease // Cell. 2017. Vol. 170, № 1. P. 17–33.Simanshu D.K., Nissley D.V., McCormick F. RAS Proteins and Their Regulators in Human Disease // Cell. 2017. Vol. 170, № 1. P. 17–33.Dias Carvalho P. et al. KRAS Oncogenic Signaling Extends beyond Cancer Cells to Orchestrate the Microenvironment // Cancer Res. 2018. Vol. 78, № 1. P. 7–14.Dias Carvalho P. et al. KRAS Oncogenic Signaling Extends beyond Cancer Cells to Orchestrate the Microenvironment // Cancer Res. 2018. Vol. 78, № 1. P. 7–14.Ros J. et al. The Evolving Role of Consensus Molecular Subtypes: a Step Beyond Inpatient Selection for Treatment of Colorectal Cancer // Curr. Treat. Options Oncol. 2021. Vol. 22, № 12. P. 113.Ros J. et al. The Evolving Role of Consensus Molecular Subtypes: a Step Beyond Inpatient Selection for Treatment of Colorectal Cancer // Curr. Treat. Options Oncol. 2021. Vol. 22, № 12. P. 113.Irahara N. et al. NRAS mutations are rare in colorectal cancer // Diagn. Mol. Pathol. Am.J. Surg. Pathol. Part B. 2010. Vol. 19, № 3. P. 157–163.Irahara N. et al. NRAS mutations are rare in colorectal cancer // Diagn. Mol. Pathol. Am.J. Surg. Pathol. Part B. 2010. Vol. 19, № 3. P. 157–163.Bos J.L. et al. Prevalence of ras gene mutations in human colorectal cancers // Nature. 1987. Vol. 327, № 6120. P. 293–297.Bos J.L. et al. Prevalence of ras gene mutations in human colorectal cancers // Nature. 1987. Vol. 327, № 6120. P. 293–297.Cefalì M. et al. Research progress on KRAS mutations in colorectal cancer // J. Cancer Metastasis Treat. OAE Publishing Inc., 2021. Vol. 7. P. 26.Cefalì M. et al. Research progress on KRAS mutations in colorectal cancer // J. Cancer Metastasis Treat. OAE Publishing Inc., 2021. Vol. 7. P. 26.Miller M.S., Miller L.D. RAS Mutations and Oncogenesis: Not all RAS Mutations are Created Equally // Front. Genet. 2012. Vol. 2. P. 100.Miller M.S., Miller L.D. RAS Mutations and Oncogenesis: Not all RAS Mutations are Created Equally // Front. Genet. 2012. Vol. 2. P. 100.Hunter J.C. et al. Biochemical and Structural Analysis of Common Cancer-Associated KRAS Mutations // Mol. Cancer Res. MCR. 2015. Vol. 13, № 9. P. 1325–1335.Hunter J.C. et al. Biochemical and Structural Analysis of Common Cancer-Associated KRAS Mutations // Mol. Cancer Res. MCR. 2015. Vol. 13, № 9. P. 1325–1335.Smith M.J., Neel B.G., Ikura M. NMR-based functional profiling of RASopathies and oncogenic RAS mutations // Proc. Natl. Acad. Sci. U. S. A. 2013. Vol. 110, № 12. P. 4574–4579.Smith M.J., Neel B.G., Ikura M. NMR-based functional profiling of RASopathies and oncogenic RAS mutations // Proc. Natl. Acad. Sci. U. S. A. 2013. Vol. 110, № 12. P. 4574–4579.Feig L.A., Cooper G.M. Relationship among guanine nucleotide exchange, GTP hydrolysis, and transforming potential of mutated ras proteins // Mol. Cell. Biol. 1988. Vol. 8, № 6. P. 2472–2478.Feig L.A., Cooper G.M. Relationship among guanine nucleotide exchange, GTP hydrolysis, and transforming potential of mutated ras proteins // Mol. Cell. Biol. 1988. Vol. 8, № 6. P. 2472–2478.Janakiraman M. et al. Genomic and biological characterization of exon 4 KRAS mutations in human cancer // Cancer Res. 2010. Vol. 70, № 14. P. 5901–5911.Janakiraman M. et al. Genomic and biological characterization of exon 4 KRAS mutations in human cancer // Cancer Res. 2010. Vol. 70, № 14. P. 5901–5911.Cook J.H. et al. The origins and genetic interactions of KRAS mutations are allele- and tissue-specific: 1 // Nat. Commun. Nature Publishing Group, 2021. Vol. 12, № 1. P. 1808.Cook J.H. et al. The origins and genetic interactions of KRAS mutations are allele- and tissue-specific: 1 // Nat. Commun. Nature Publishing Group, 2021. Vol. 12, № 1. P. 1808.De Roock W. et al. Association of KRAS p.G13D mutation with outcome in patients with chemotherapy-refractory metastatic colorectal cancer treated with cetuximab // JAMA. 2010. Vol. 304, № 16. P. 1812–1820.De Roock W. et al. Association of KRAS p.G13D mutation with outcome in patients with chemotherapy-refractory metastatic colorectal cancer treated with cetuximab // JAMA. 2010. Vol. 304, № 16. P. 1812–1820.Serebriiskii I.G. et al. Comprehensive characterization of RAS mutations in colon and rectal cancers in old and young patients // Nat. Commun. 2019. Vol. 10, № 1. P. 3722.Serebriiskii I.G. et al. Comprehensive characterization of RAS mutations in colon and rectal cancers in old and young patients // Nat. Commun. 2019. Vol. 10, № 1. P. 3722.Goebel L. et al. KRasG12C inhibitors in clinical trials: a short historical perspective // RSC Med. Chem. RSC, 2020. Vol. 11, № 7. P. 760–770.Goebel L. et al. KRasG12C inhibitors in clinical trials: a short historical perspective // RSC Med. Chem. RSC, 2020. Vol. 11, № 7. P. 760–770.Chida K. et al. The Prognostic Impact of KRAS G12C Mutation in Patients with Metastatic Colorectal Cancer: A Multicenter Retrospective Observational Study // The Oncologist. 2021. Vol. 26, № 10. P. 845–853.Chida K. et al. The Prognostic Impact of KRAS G12C Mutation in Patients with Metastatic Colorectal Cancer: A Multicenter Retrospective Observational Study // The Oncologist. 2021. Vol. 26, № 10. P. 845–853.Masuishi T. et al. 444TiP Trial in progress: A phase Ib study of sotorasib, a selective KRAS G12C inhibitor, in combination with panitumumab and FOLFIRI in treatment naïve and previously treated metastatic colorectal cancer (CodeBreaK 101) // Ann. Oncol. Elsevier, 2022. Vol. 33. P. S737–S738.Masuishi T. et al. 444TiP Trial in progress: A phase Ib study of sotorasib, a selective KRAS G12C inhibitor, in combination with panitumumab and FOLFIRI in treatment naïve and previously treated metastatic colorectal cancer (CodeBreaK 101) // Ann. Oncol. Elsevier, 2022. Vol. 33. P. S737–S738.Yaeger R. et al. Adagrasib with or without Cetuximab in Colorectal Cancer with Mutated KRAS G12C // N. Engl. J. Med. 2023. Vol. 388, № 1. P. 44–54.Yaeger R. et al. Adagrasib with or without Cetuximab in Colorectal Cancer with Mutated KRAS G12C // N. Engl. J. Med. 2023. Vol. 388, № 1. P. 44–54.Overman M.J. et al. Use of research biopsies in clinical trials: are risks and benefits adequately discussed? // J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol. 2013. Vol. 31, № 1. P. 17–22.Overman M.J. et al. Use of research biopsies in clinical trials: are risks and benefits adequately discussed? // J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol. 2013. Vol. 31, № 1. P. 17–22.Venesio T. et al. Liquid Biopsies for Monitoring Temporal Genomic Heterogeneity in Breast and Colon Cancers // Pathobiology. Karger Publishers, 2018. Vol. 85, № 1–2. P. 146–154.Venesio T. et al. Liquid Biopsies for Monitoring Temporal Genomic Heterogeneity in Breast and Colon Cancers // Pathobiology. Karger Publishers, 2018. Vol. 85, № 1–2. P. 146–154.Udagawa S. et al. Circulating Tumor DNA: The Dawn of a New Era in the Optimization of Chemotherapeutic Strategies for Metastatic Colo-Rectal Cancer Focusing on RAS Mutation: 5 // Cancers. Multidisciplinary Digital Publishing Institute, 2023. Vol. 15, № 5. P. 1473.Udagawa S. et al. Circulating Tumor DNA: The Dawn of a New Era in the Optimization of Chemotherapeutic Strategies for Metastatic Colo-Rectal Cancer Focusing on RAS Mutation: 5 // Cancers. Multidisciplinary Digital Publishing Institute, 2023. Vol. 15, № 5. P. 1473.Malla M. et al. Using Circulating Tumor DNA in Colorectal Cancer: Current and Evolving Practices // J. Clin. Oncol. Wolters Kluwer, 2022. Vol. 40, № 24. P. 2846–2857Malla M. et al. Using Circulating Tumor DNA in Colorectal Cancer: Current and Evolving Practices // J. Clin. Oncol. Wolters Kluwer, 2022. Vol. 40, № 24. P. 2846–2857Patelli G. et al. Liquid Biopsy for Prognosis and Treatment in Metastatic Colorectal Cancer: Circulating Tumor Cells vs Circulating Tumor DNA // Target. Oncol. 2021. Vol. 16, № 3. P. 309–324.Patelli G. et al. Liquid Biopsy for Prognosis and Treatment in Metastatic Colorectal Cancer: Circulating Tumor Cells vs Circulating Tumor DNA // Target. Oncol. 2021. Vol. 16, № 3. P. 309–324.Nagayama S. et al. Precision Medicine for Colorectal Cancer with Liquid Biopsy and Immunotherapy: 19 // Cancers. Multidisciplinary Digital Publishing Institute, 2021. Vol. 13, № 19. P. 4803.Nagayama S. et al. Precision Medicine for Colorectal Cancer with Liquid Biopsy and Immunotherapy: 19 // Cancers. Multidisciplinary Digital Publishing Institute, 2021. Vol. 13, № 19. P. 4803.Mazouji O. et al. Updates on Clinical Use of Liquid Biopsy in Colorectal Cancer Screening, Diagnosis, Follow-Up, and Treatment Guidance // Front. Cell Dev. Biol. 2021. Vol. 9. P. 660924.Mazouji O. et al. Updates on Clinical Use of Liquid Biopsy in Colorectal Cancer Screening, Diagnosis, Follow-Up, and Treatment Guidance // Front. Cell Dev. Biol. 2021. Vol. 9. P. 660924.Mauri G. et al. Liquid biopsies to monitor and direct cancer treatment in colorectal cancer: 3 // Br.J. Cancer. Nature Publishing Group, 2022. Vol. 127, № 3. P. 394–407.Mauri G. et al. Liquid biopsies to monitor and direct cancer treatment in colorectal cancer: 3 // Br.J. Cancer. Nature Publishing Group, 2022. Vol. 127, № 3. P. 394–407.Tr A. A case of cancer in which cells similar to those in the tumours were seen in the blood after death // Aust Med J. 1869. Vol. 14. P. 146.Tr A. A case of cancer in which cells similar to those in the tumours were seen in the blood after death // Aust Med J. 1869. Vol. 14. P. 146.Stroun M. et al. Neoplastic Characteristics of the DNA Found in the Plasma of Cancer Patients // Oncology. Karger Publishers, 1989. Vol. 46, № 5. P. 318–322.Stroun M. et al. Neoplastic Characteristics of the DNA Found in the Plasma of Cancer Patients // Oncology. Karger Publishers, 1989. Vol. 46, № 5. P. 318–322.Diaz L.A., Bardelli A. Liquid biopsies: genotyping circulating tumor DNA // J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol. 2014. Vol. 32, № 6. P. 579–586.Diaz L.A., Bardelli A. Liquid biopsies: genotyping circulating tumor DNA // J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol. 2014. Vol. 32, № 6. P. 579–586.Siravegna G. et al. Integrating liquid biopsies into the management of cancer // Nat. Rev. Clin. Oncol. 2017. Vol. 14, № 9. P. 531–548.Siravegna G. et al. Integrating liquid biopsies into the management of cancer // Nat. Rev. Clin. Oncol. 2017. Vol. 14, № 9. P. 531–548.Downing A. et al. High hospital research participation and improved colorectal cancer survival outcomes: a population-based study // Gut. 2017. Vol. 66, № 1. P. 89–96.Downing A. et al. High hospital research participation and improved colorectal cancer survival outcomes: a population-based study // Gut. 2017. Vol. 66, № 1. P. 89–96.Antoniotti C. et al. Circulating Tumor DNA Analysis in Colorectal Cancer: From Dream to Reality // JCO Precis. Oncol. 2019. Vol. 3. P. 1–14.Antoniotti C. et al. Circulating Tumor DNA Analysis in Colorectal Cancer: From Dream to Reality // JCO Precis. Oncol. 2019. Vol. 3. P. 1–14.Wan J.C.M. et al. ctDNA monitoring using patient-specific sequencing and integration of variant reads // Sci. Transl. Med. 2020. Vol. 12, № 548. P. eaaz8084.Wan J.C.M. et al. ctDNA monitoring using patient-specific sequencing and integration of variant reads // Sci. Transl. Med. 2020. Vol. 12, № 548. P. eaaz8084.Chen Q. et al. Circulating Cell-Free DNA or Circulating Tumor DNA in the Management of Ovarian and Endometrial Cancer // OncoTargets Ther. 2019. Vol. 12. P. 11517–11530.Chen Q. et al. Circulating Cell-Free DNA or Circulating Tumor DNA in the Management of Ovarian and Endometrial Cancer // OncoTargets Ther. 2019. Vol. 12. P. 11517–11530.Mouliere F., Thierry A.R. The importance of examining the proportion of circulating DNA originating from tumor, microenvironment and normal cells in colorectal cancer patients // Expert Opin. Biol. Ther. 2012. Vol. 12 Suppl 1. P. S209–215.Mouliere F., Thierry A.R. The importance of examining the proportion of circulating DNA originating from tumor, microenvironment and normal cells in colorectal cancer patients // Expert Opin. Biol. Ther. 2012. Vol. 12 Suppl 1. P. S209–215.Leon S.A. et al. Free DNA in the Serum of Cancer Patients and the Effect of Therapy // Cancer Res. 1977. Vol. 37, № 3. P. 646–650.Leon S.A. et al. Free DNA in the Serum of Cancer Patients and the Effect of Therapy // Cancer Res. 1977. Vol. 37, № 3. P. 646–650.Bettegowda C. et al. Detection of circulating tumor DNA in early- and late-stage human malignancies // Sci. Transl. Med. 2014. Vol. 6, № 224. P. 224ra24.Bettegowda C. et al. Detection of circulating tumor DNA in early- and late-stage human malignancies // Sci. Transl. Med. 2014. Vol. 6, № 224. P. 224ra24.Avanzini S. et al. A mathematical model of ctDNA shedding predicts tumor detection size // Sci. Adv. American Association for the Advancement of Science, 2020. Vol. 6, № 50. P. eabc4308.Avanzini S. et al. A mathematical model of ctDNA shedding predicts tumor detection size // Sci. Adv. American Association for the Advancement of Science, 2020. Vol. 6, № 50. P. eabc4308.Forshew T. et al. Noninvasive identification and monitoring of cancer mutations by targeted deep sequencing of plasma DNA // Sci. Transl. Med. 2012. Vol. 4, № 136. P. 136ra68.Forshew T. et al. Noninvasive identification and monitoring of cancer mutations by targeted deep sequencing of plasma DNA // Sci. Transl. Med. 2012. Vol. 4, № 136. P. 136ra68.Buono G. et al. Circulating tumor DNA analysis in breast cancer: Is it ready for prime-time? // Cancer Treat. Rev. 2019. Vol. 73. P. 73–83.Buono G. et al. Circulating tumor DNA analysis in breast cancer: Is it ready for prime-time? // Cancer Treat. Rev. 2019. Vol. 73. P. 73–83.Barlebo Ahlborn L., Østrup O. Toward liquid biopsies in cancer treatment: application of circulating tumor DNA // APMIS Acta Pathol. Microbiol. Immunol. Scand. 2019. Vol. 127, № 5. P. 329–336.Barlebo Ahlborn L., Østrup O. Toward liquid biopsies in cancer treatment: application of circulating tumor DNA // APMIS Acta Pathol. Microbiol. Immunol. Scand. 2019. Vol. 127, № 5. P. 329–336.Wu J. et al. Tumor circulome in the liquid biopsies for cancer diagnosis and prognosis // Theranostics. 2020. Vol. 10, № 10. P. 4544–4556.Wu J. et al. Tumor circulome in the liquid biopsies for cancer diagnosis and prognosis // Theranostics. 2020. Vol. 10, № 10. P. 4544–4556.Osumi H. et al. Clinical utility of circulating tumor DNA for colorectal cancer // Cancer Sci. 2019. Vol. 110, № 4. P. 1148–1155.Osumi H. et al. Clinical utility of circulating tumor DNA for colorectal cancer // Cancer Sci. 2019. Vol. 110, № 4. P. 1148–1155.Li H. et al. Circulating tumor DNA detection: A potential tool for colorectal cancer management (Review) // Oncol. Lett. Spandidos Publications, 2019. Vol. 17, № 2. P. 1409–1416.Li H. et al. Circulating tumor DNA detection: A potential tool for colorectal cancer management (Review) // Oncol. Lett. Spandidos Publications, 2019. Vol. 17, № 2. P. 1409–1416.Nikanjam M., Kato S., Kurzrock R. Liquid biopsy: current technology and clinical applications // J. Hematol. Oncol.J Hematol Oncol. 2022. Vol. 15, № 1. P. 131.Nikanjam M., Kato S., Kurzrock R. Liquid biopsy: current technology and clinical applications // J. Hematol. Oncol.J Hematol Oncol. 2022. Vol. 15, № 1. P. 131.García-Foncillas J. et al. Prospective multicenter real-world RAS mutation comparison between OncoBEAM-based liquid biopsy and tissue analysis in metastatic colorectal cancer: 12 // Br.J. Cancer. Nature Publishing Group, 2018. Vol. 119, № 12. P. 1464–1470.García-Foncillas J. et al. Prospective multicenter real-world RAS mutation comparison between OncoBEAM-based liquid biopsy and tissue analysis in metastatic colorectal cancer: 12 // Br.J. Cancer. Nature Publishing Group, 2018. Vol. 119, № 12. P. 1464–1470.Vessies D.C.L. et al. Performance of four platforms for KRAS mutation detection in plasma cell-free DNA: ddPCR, Idylla, COBAS z480 and BEAMing // Sci. Rep. 2020. Vol. 10, № 1. P. 8122.Vessies D.C.L. et al. Performance of four platforms for KRAS mutation detection in plasma cell-free DNA: ddPCR, Idylla, COBAS z480 and BEAMing // Sci. Rep. 2020. Vol. 10, № 1. P. 8122.Garcia J. et al. Cross-platform comparison for the detection of RAS mutations in cfDNA (ddPCR Biorad detection assay, BEAMing assay, and NGS strategy) // Oncotarget. 2018. Vol. 9, № 30. P. 21122–21131.Garcia J. et al. Cross-platform comparison for the detection of RAS mutations in cfDNA (ddPCR Biorad detection assay, BEAMing assay, and NGS strategy) // Oncotarget. 2018. Vol. 9, № 30. P. 21122–21131.Siravegna G. et al. How liquid biopsies can change clinical practice in oncology // Ann. Oncol. 2019. Vol. 30, № 10. P. 1580–1590.Siravegna G. et al. How liquid biopsies can change clinical practice in oncology // Ann. Oncol. 2019. Vol. 30, № 10. P. 1580–1590.Kamps R. et al. Next-Generation Sequencing in Oncology: Genetic Diagnosis, Risk Prediction and Cancer Classification: 2 // Int. J. Mol. Sci. Multidisciplinary Digital Publishing Institute, 2017. Vol. 18, № 2. P. 308.Kamps R. et al. Next-Generation Sequencing in Oncology: Genetic Diagnosis, Risk Prediction and Cancer Classification: 2 // Int. J. Mol. Sci. Multidisciplinary Digital Publishing Institute, 2017. Vol. 18, № 2. P. 308.Bennouna J. et al. Continuation of bevacizumab after first progression in metastatic colorectal cancer (ML18147): a randomised phase 3 trial // Lancet Oncol. 2013. Vol. 14, № 1. P. 29–37.Bennouna J. et al. Continuation of bevacizumab after first progression in metastatic colorectal cancer (ML18147): a randomised phase 3 trial // Lancet Oncol. 2013. Vol. 14, № 1. P. 29–37.Ciardiello D. et al. Pretreatment Plasma Circulating Tumor DNA RAS/BRAF Mutational Status in Refractory Metastatic Colorectal Cancer Patients Who Are Candidates for Anti-EGFR Rechallenge Therapy: A Pooled Analysis of the CAVE and VELO Clinical Trials: 7 // Cancers. Multidisciplinary Digital Publishing Institute, 2023. Vol. 15, № 7. P. 2117.Ciardiello D. et al. Pretreatment Plasma Circulating Tumor DNA RAS/BRAF Mutational Status in Refractory Metastatic Colorectal Cancer Patients Who Are Candidates for Anti-EGFR Rechallenge Therapy: A Pooled Analysis of the CAVE and VELO Clinical Trials: 7 // Cancers. Multidisciplinary Digital Publishing Institute, 2023. Vol. 15, № 7. P. 2117.Grothey A. et al. Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial // The Lancet. 2013. Vol. 381, № 9863. P. 303–312.Grothey A. et al. Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial // The Lancet. 2013. Vol. 381, № 9863. P. 303–312.Mayer R.J. et al. Randomized Trial of TAS-102 for Refractory Metastatic Colorectal Cancer // N. Engl. J. Med. Massachusetts Medical Society, 2015. Vol. 372, № 20. P. 1909–1919.Mayer R.J. et al. Randomized Trial of TAS-102 for Refractory Metastatic Colorectal Cancer // N. Engl. J. Med. Massachusetts Medical Society, 2015. Vol. 372, № 20. P. 1909–1919.Li J. et al. Regorafenib plus best supportive care versus placebo plus best supportive care in Asian patients with previously treated metastatic colorectal cancer (CONCUR): a randomised, double-blind, placebo-controlled, phase 3 trial // Lancet Oncol. 2015. Vol. 16, № 6. P. 619–629.Li J. et al. Regorafenib plus best supportive care versus placebo plus best supportive care in Asian patients with previously treated metastatic colorectal cancer (CONCUR): a randomised, double-blind, placebo-controlled, phase 3 trial // Lancet Oncol. 2015. Vol. 16, № 6. P. 619–629.Ciardiello D. et al. Biomarker-Guided Anti-EGFR Rechallenge Therapy in Metastatic Colorectal Cancer: 8 // Cancers. Multidisciplinary Digital Publishing Institute, 2021. Vol. 13, № 8. P. 1941.Ciardiello D. et al. Biomarker-Guided Anti-EGFR Rechallenge Therapy in Metastatic Colorectal Cancer: 8 // Cancers. Multidisciplinary Digital Publishing Institute, 2021. Vol. 13, № 8. P. 1941.Avallone A. et al. Randomized intermittent or continuous panitumumab plus FOLFIRI (FOLFIRI/ PANI) for first-line treatment of patients (pts) with RAS/BRAF wild-type (wt) metastatic colorectal cancer (mCRC): The IMPROVE study. // J. Clin. Oncol. Wolters Kluwer, 2022. Vol. 40, № 16_suppl. P. 3503–3503.Avallone A. et al. Randomized intermittent or continuous panitumumab plus FOLFIRI (FOLFIRI/ PANI) for first-line treatment of patients (pts) with RAS/BRAF wild-type (wt) metastatic colorectal cancer (mCRC): The IMPROVE study. // J. Clin. Oncol. Wolters Kluwer, 2022. Vol. 40, № 16_suppl. P. 3503–3503.Misale S. et al. Emergence of KRAS mutations and acquired resistance to anti-EGFR therapy in colorectal cancer: 7404 // Nature. Nature Publishing Group, 2012. Vol. 486, № 7404. P. 532–536.Misale S. et al. Emergence of KRAS mutations and acquired resistance to anti-EGFR therapy in colorectal cancer: 7404 // Nature. Nature Publishing Group, 2012. Vol. 486, № 7404. P. 532–536.Diaz Jr L.A. et al. The molecular evolution of acquired resistance to targeted EGFR blockade in colorectal cancers: 7404 // Nature. Nature Publishing Group, 2012. Vol. 486, № 7404. P. 537–540.Diaz Jr L.A. et al. The molecular evolution of acquired resistance to targeted EGFR blockade in colorectal cancers: 7404 // Nature. Nature Publishing Group, 2012. Vol. 486, № 7404. P. 537–540.Cremolini C. et al. Rechallenge with anti-EGFR therapy to extend the continuum of care in patients with metastatic colorectal cancer // Front. Oncol. 2023. Vol. 12.Cremolini C. et al. Rechallenge with anti-EGFR therapy to extend the continuum of care in patients with metastatic colorectal cancer // Front. Oncol. 2023. Vol. 12.Osawa H. et al. Phase II study of cetuximab rechallenge in patients with ras wild-type metastatic colorectal cancer: E-rechallenge trial // Ann. Oncol. Elsevier, 2018. Vol. 29. P. viii161.Osawa H. et al. Phase II study of cetuximab rechallenge in patients with ras wild-type metastatic colorectal cancer: E-rechallenge trial // Ann. Oncol. Elsevier, 2018. Vol. 29. P. viii161.Martinelli E. et al. Cetuximab Rechallenge Plus Avelumab in Pretreated Patients With RAS Wild-type Metastatic Colorectal Cancer: The Phase 2 Single-Arm Clinical CAVE Trial // JAMA Oncol. 2021. Vol. 7, № 10. P. 1529–1535.Martinelli E. et al. Cetuximab Rechallenge Plus Avelumab in Pretreated Patients With RAS Wild-type Metastatic Colorectal Cancer: The Phase 2 Single-Arm Clinical CAVE Trial // JAMA Oncol. 2021. Vol. 7, № 10. P. 1529–1535.Sartore-Bianchi A. et al. Circulating tumor DNA to guide rechallenge with panitumumab in metastatic colorectal cancer: the phase 2 CHRONOS trial: 8 // Nat. Med. Nature Publishing Group, 2022. Vol. 28, № 8. P. 1612–1618.Sartore-Bianchi A. et al. Circulating tumor DNA to guide rechallenge with panitumumab in metastatic colorectal cancer: the phase 2 CHRONOS trial: 8 // Nat. Med. Nature Publishing Group, 2022. Vol. 28, № 8. P. 1612–1618.Kagawa Y. et al. Plasma RAS dynamics and anti-EGFR rechallenge efficacy in patients with RAS/BRAF wild-type metastatic colorectal cancer: REMARRY and PURSUIT trials. // J. Clin. Oncol. Wolters Kluwer, 2022. Vol. 40, № 16_suppl. P. 3518–3518.Kagawa Y. et al. Plasma RAS dynamics and anti-EGFR rechallenge efficacy in patients with RAS/BRAF wild-type metastatic colorectal cancer: REMARRY and PURSUIT trials. // J. Clin. Oncol. Wolters Kluwer, 2022. Vol. 40, № 16_suppl. P. 3518–3518.Sugimachi K. et al. Serial mutational tracking in surgically resected locally advanced colorectal cancer with neoadjuvant chemotherapy: 4 // Br.J. Cancer. Nature Publishing Group, 2018. Vol. 119, № 4. P. 419–423.Sugimachi K. et al. Serial mutational tracking in surgically resected locally advanced colorectal cancer with neoadjuvant chemotherapy: 4 // Br.J. Cancer. Nature Publishing Group, 2018. Vol. 119, № 4. P. 419–423.Klein-Scory S. et al. Evolution of RAS Mutational Status in Liquid Biopsies During First-Line Chemotherapy for Metastatic Colorectal Cancer // Front. Oncol. 2020. Vol. 10.Klein-Scory S. et al. Evolution of RAS Mutational Status in Liquid Biopsies During First-Line Chemotherapy for Metastatic Colorectal Cancer // Front. Oncol. 2020. Vol. 10.Raimondi C. et al. Transient Disappearance of RAS Mutant Clones in Plasma: A Counterintuitive Clinical Use of EGFR Inhibitors in RAS Mutant Metastatic Colorectal Cancer: 1 // Cancers. Multidisciplinary Digital Publishing Institute, 2019. Vol. 11, № 1. P. 42.Raimondi C. et al. Transient Disappearance of RAS Mutant Clones in Plasma: A Counterintuitive Clinical Use of EGFR Inhibitors in RAS Mutant Metastatic Colorectal Cancer: 1 // Cancers. Multidisciplinary Digital Publishing Institute, 2019. Vol. 11, № 1. P. 42.Ma X. et al. Rise and fall of subclones from diagnosis to relapse in pediatric B-acute lymphoblastic leukaemia: 1 // Nat. Commun. Nature Publishing Group, 2015. Vol. 6, № 1. P. 6604.Ma X. et al. Rise and fall of subclones from diagnosis to relapse in pediatric B-acute lymphoblastic leukaemia: 1 // Nat. Commun. Nature Publishing Group, 2015. Vol. 6, № 1. P. 6604.Nicolazzo C. et al. Circulating Methylated DNA to Monitor the Dynamics of RAS Mutation Clearance in Plasma from Metastatic Colorectal Cancer Patients: 12 // Cancers. Multidisciplinary Digital Publishing Institute, 2020. Vol. 12, № 12. P. 3633.Nicolazzo C. et al. Circulating Methylated DNA to Monitor the Dynamics of RAS Mutation Clearance in Plasma from Metastatic Colorectal Cancer Patients: 12 // Cancers. Multidisciplinary Digital Publishing Institute, 2020. Vol. 12, № 12. P. 3633.Moati E. et al. Plasma clearance of RAS mutation under therapeutic pressure is a rare event in metastatic colorectal cancer // Int. J. Cancer. 2020. Vol. 147, № 4. P. 1185–1189.Moati E. et al. Plasma clearance of RAS mutation under therapeutic pressure is a rare event in metastatic colorectal cancer // Int. J. Cancer. 2020. Vol. 147, № 4. P. 1185–1189.Henry J. et al. NeoRAS: Incidence of RAS reversion from RAS mutated to RAS wild type. // J. Clin. Oncol. Wolters Kluwer, 2020. Vol. 38, № 4_suppl. P. 180–180.Henry J. et al. NeoRAS: Incidence of RAS reversion from RAS mutated to RAS wild type. // J. Clin. Oncol. Wolters Kluwer, 2020. Vol. 38, № 4_suppl. P. 180–180.Nicolazzo C. et al. True conversions from RAS mutant to RAS wild-type in circulating tumor DNA from metastatic colorectal cancer patients as assessed by methylation and mutational signature // Cancer Lett. 2021. Vol. 507. P. 89–96.Nicolazzo C. et al. True conversions from RAS mutant to RAS wild-type in circulating tumor DNA from metastatic colorectal cancer patients as assessed by methylation and mutational signature // Cancer Lett. 2021. Vol. 507. P. 89–96.Bouchahda M. et al. Undetectable RAS-Mutant Clones in Plasma: Possible Implication for Anti-EGFR Therapy and Prognosis in Patients With RAS-Mutant Metastatic Colorectal Cancer // JCO Precis. Oncol. Wolters Kluwer, 2020. № 4. P. 1070–1079.Bouchahda M. et al. Undetectable RAS-Mutant Clones in Plasma: Possible Implication for Anti-EGFR Therapy and Prognosis in Patients With RAS-Mutant Metastatic Colorectal Cancer // JCO Precis. Oncol. Wolters Kluwer, 2020. № 4. P. 1070–1079.Sunakawa Y. et al. Dynamic changes in RAS gene status in circulating tumour DNA: a phase II trial of first-line FOLFOXIRI plus bevacizumab for RAS-mutant metastatic colorectal cancer (JACCRO CC-11) // ESMO Open. 2022. Vol. 7, № 3. P. 100512.Sunakawa Y. et al. Dynamic changes in RAS gene status in circulating tumour DNA: a phase II trial of first-line FOLFOXIRI plus bevacizumab for RAS-mutant metastatic colorectal cancer (JACCRO CC-11) // ESMO Open. 2022. Vol. 7, № 3. P. 100512.Nicolazzo C. et al. RAS Mutation Conversion in Bevacizumab-Treated Metastatic Colorectal Cancer Patients: A Liquid Biopsy Based Study // Cancers. 2022. Vol. 14, № 3. P. 802.Nicolazzo C. et al. RAS Mutation Conversion in Bevacizumab-Treated Metastatic Colorectal Cancer Patients: A Liquid Biopsy Based Study // Cancers. 2022. Vol. 14, № 3. P. 802.Sunakawa Y. et al. Gene mutation status in circulating tumor DNA (ctDNA) and first-line FOLFOXIRI plus bevacizumab (bev) in metastatic colorectal cancer (mCRC) harboring RAS mutation // Ann. Oncol. Elsevier, 2018. Vol. 29. P. viii181–viii182.Sunakawa Y. et al. Gene mutation status in circulating tumor DNA (ctDNA) and first-line FOLFOXIRI plus bevacizumab (bev) in metastatic colorectal cancer (mCRC) harboring RAS mutation // Ann. Oncol. Elsevier, 2018. Vol. 29. P. viii181–viii182.DE Santiago B.G. et al. RAS Mutational Status in Advanced Colorectal Adenocarcinoma Treated With Anti-angiogenics: Preliminary Experience With Liquid Biopsy // Vivo Athens Greece. 2021. Vol. 35, № 5. P. 2841–2844.DE Santiago B.G. et al. RAS Mutational Status in Advanced Colorectal Adenocarcinoma Treated With Anti-angiogenics: Preliminary Experience With Liquid Biopsy // Vivo Athens Greece. 2021. Vol. 35, № 5. P. 2841–2844.Parsons B.L., Myers M.B. Personalized cancer treatment and the myth of KRAS wild-type colon tumors // Discov. Med. 2013. Vol. 15, № 83. P. 259–267.Parsons B.L., Myers M.B. Personalized cancer treatment and the myth of KRAS wild-type colon tumors // Discov. Med. 2013. Vol. 15, № 83. P. 259–267.Epistolio S. et al. Occurence of RAS reversion in metastatic colorectal cancer patients treated with bevacizumab // Oncotarget. 2021. Vol. 12, № 11. P. 1046–1056.Epistolio S. et al. Occurence of RAS reversion in metastatic colorectal cancer patients treated with bevacizumab // Oncotarget. 2021. Vol. 12, № 11. P. 1046–1056.Bartolacci C. et al. Lipid Metabolism Regulates Oxidative Stress and Ferroptosis in RAS-Driven Cancers: A Perspective on Cancer Progression and Therapy // Front. Mol. Biosci. 2021. Vol. 8. P. 706650.Bartolacci C. et al. Lipid Metabolism Regulates Oxidative Stress and Ferroptosis in RAS-Driven Cancers: A Perspective on Cancer Progression and Therapy // Front. Mol. Biosci. 2021. Vol. 8. P. 706650.Lim J.K.M., Leprivier G. The impact of oncogenic RAS on redox balance and implications for cancer development: 12 // Cell Death Dis. Nature Publishing Group, 2019. Vol. 10, № 12. P. 1–9.Lim J.K.M., Leprivier G. The impact of oncogenic RAS on redox balance and implications for cancer development: 12 // Cell Death Dis. Nature Publishing Group, 2019. Vol. 10, № 12. P. 1–9.Xu W., Trepel J., Neckers L. Ras, ROS and proteotoxic stress: a delicate balance // Cancer Cell. 2011. Vol. 20, № 3. P. 281–282.Xu W., Trepel J., Neckers L. Ras, ROS and proteotoxic stress: a delicate balance // Cancer Cell. 2011. Vol. 20, № 3. P. 281–282.

The authors declare that there are no conflicts of interest present.