cancerspЮжно-Российский онкологический журнал/ South Russian Journal of CancerSouth Russian Journal of Cancer2686-9039АНО "Перспективы онкологии"10.37748/2686-9039-2021-2-2-6cancersp-94Research ArticleОБЗОРЫREVIEWSМолекулярно-генетическая классификация подтипов колоректального рака: современное состояние проблемыMolecular genetic classification of colorectal cancer subtypes: current state of the problemhttps://orcid.org/0000-0003-3061-6108КитО. И.KitO. I.

Кит Олег Иванович – член-корр. РАН, д.м.н., профессор, генеральный директор. SPIN: 1728-0329, AuthorID: 343182, ResearcherID: U-2241-2017, Scopus Author ID: 55994103100

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Oleg I. Kit – member of Russian Academy of Sciences, Dr. Sci. (Med.), professor, general director. SPIN: 1728-0329, AuthorID: 343182, ResearcherID: U-2241-2017, Scopus Author ID: 55994103100

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onko-sekretar@mail.ruhttps://orcid.org/0000-0002-3561-098XДженковаЕ. А.DzhenkovaE. A.

Дженкова Елена Алексеевна – д.м.н., доцент, ученый секретарь ученого совета.  SPIN: 6206-6222, AuthorID: 697354, ResearcherID: K-9622-2014, Scopus Author ID: 6507889745

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Elena A. Dzhenkova – Dr. Sci. (Med.), Associate Professor, academic secretary of the Academic Council. SPIN: 6206-6222, AuthorID: 697354, ResearcherID: K-9622-2014, Scopus Author ID: 6507889745

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rnioi@list.ruhttps://orcid.org/0000-0002-0328-9714МирзоянЭ. А.MirzoyanE. A.

Мирзоян Эллада Арменовна – аспирант ФГБУ «НМИЦ онкологии» Минздрава России. SPIN: 2506-8605, AuthorID: 1002948

Ellada A. Mirzoyan – PhD student. SPIN: 2506-8605, AuthorID: 1002948

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ellada.mirzoyan@yandex.ruhttps://orcid.org/0000-0003-1957-7363ГеворкянЮ. А.GevorkyanYu. A.

Геворкян Юрий Артушевич – д.м.н., профессор, заведующий отделением абдоминальной онкологии №2. SPIN: 8643-2348, AuthorID: 711165

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Yuriy A. Gevorkyan – Dr. Sci. (Med.), professor, Head of the Department of Abdominal Oncology No. 2. SPIN: 8643-2348, AuthorID: 711165

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gevorkyan.000@mail.ruhttps://orcid.org/0000-0003-0874-5261СагакянцА. Б.SagakyantsA. B.

Сагакянц Александр Борисович – к.б.н., доцент, заведующий лабораторией иммунофенотипирования опухолей. SPIN: 7272-1408, AuthorID: 426904, ResearcherID: M-8378-2019, Scopus Author ID: 24329773900

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Aleksandr B. Sagakyants – Cand. Sci. (Biol.), associate Professor, Head of the Laboratory of Tumor Immunophenotyping. SPIN: 7272-1408, AuthorID: 426904, ResearcherID: M-8378-2019, Scopus Author ID: 24329773900

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asagak@rambler.ruhttps://orcid.org/0000-0001-6358-7361ТимошкинаН. Н.TimoshkinaN. N.

Тимошкина Наталья Николаевна – к.б.н. заведующая лабораторией молекулярной онкологии. SPIN: 9483-4330, AuthorID: 63365

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Natalia N. Timoshkina – Cand. Sci. (Biol.), head of the Laboratory of Molecular Oncology. SPIN: 9483-4330, AuthorID: 633651

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timoshkinann@rnioi.ruКаймакчиО. Ю.KaymakchiO. Yu.

Каймакчи Олег Юрьевич – д.м.н., доцент кафедры онкологии. AuthorID: 335064

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Oleg Yu. Kaymakchi – Dr. Sci. (Med.), associate Professor of Oncology Department. AuthorID: 335064

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okaymakchi@gmail.ruhttps://orcid.org/0000-0002-7556-9897КаймакчиД. О.KaymakchiD. O.

Каймакчи Дмитрий Олегович – врач-хирург отделения абдоминальной онкологии №2. SPIN: 4803-6558, AuthorID: 793912

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Dmitriy O. Kaymakchi – MD, surgeon at the Department of Abdominal Oncology No. 2. SPIN: 4803-6558, AuthorID: 793912

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dokaymakchi@mail.ruТолмахР. Е.TolmakhR. E.

Толмах Роман Евгеньевич – к.м.н., врач-хирург отделения абдоминальной онкологии №2. SPIN: 4559-2047, AuthorID: 733791

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Roman E. Tolmakh – Cand. Sci. (Med.), MD, surgeon at the Department of Abdominal Oncology No. 2. SPIN: 4559-2047, AuthorID: 733791

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tolmakh74@mail.ruhttps://orcid.org/0000-0002-3867-4532ДашковА. В.DashkovA. V.

Дашков Андрей Владимирович – к.м.н., старший научный сотрудник отделения абдоминальной онкологии №2. SPIN: 4364-9459, AuthorID: 308799

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Andrey V. Dashkov – Cand. Sci. (Med.), senior Researcher of the Department of Abdominal Oncology No. 2. SPIN: 4364-9459, AuthorID: 308799

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dashkovandrei1968@mail.ruКолесниковВ. Е.KolesnikovV. E.

Колесников Владимир Евгеньевич – д.м.н., врач-хирург отделения абдоминальной онкологии №2. SPIN: 9915-0578, AuthorID: 705852

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Vladimir E. Kolesnikov – Dr. Sci. (Med.), MD, surgeon at the Department of Abdominal Oncology №2. SPIN: 9915-0578, AuthorID: 705852

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kolaksay@yandex.ruhttps://orcid.org/0000-0001-7661-1340МилакинА. Г.MilakinA. G.

Милакин Антон Григорьевич – врач-онколог отделения торакальной онкологии. AuthorID: 794734

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Anton G. Milakin – MD, oncologist of the Department of Thoracic Oncology.  SPIN: 7737-4737, AuthorID: 794734

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amilakin@yandex.ruПолуэктовС. И.PoluektovS. I.

Полуэктов Сергей Игоревич – врач-хирург отделения абдоминальной онкологии №2. SPIN: 4267-3840, Author ID: 842869

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Sergey I. Poluektov – MD, surgeon at the Department of Abdominal Oncology No. 2. SPIN: 4267-3840, AuthorID: 842869

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PoluektovSI@yandex.ruФГБУ «НМИЦ онкологии» Минздрава РоссииРоссияNational Medical Research Centre for Oncology of the Ministry of Health of RussiaRussian Federation202118062021225056Copyright © Кит О.И., Дженкова Е.А., Мирзоян Э.А., Геворкян Ю.А., Сагакянц А.Б., Тимошкина Н.Н., Каймакчи О.Ю., Каймакчи Д.О., Толмах Р.Е., Дашков А.В., Колесников В.Е., Милакин А.Г., Полуэктов С.И., 20212021Кит О.И., Дженкова Е.А., Мирзоян Э.А., Геворкян Ю.А., Сагакянц А.Б., Тимошкина Н.Н., Каймакчи О.Ю., Каймакчи Д.О., Толмах Р.Е., Дашков А.В., Колесников В.Е., Милакин А.Г., Полуэктов С.И.Kit O.I., Dzhenkova E.A., Mirzoyan E.A., Gevorkyan Y.A., Sagakyants A.B., Timoshkina N.N., Kaymakchi O.Y., Kaymakchi D.O., Tolmakh R.E., Dashkov A.V., Kolesnikov V.E., Milakin A.G., Poluektov S.I.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.cancersp.com/jour/article/view/94

На сегодняшний день колоректальный рак (КРР) является актуальной проблемой онкологии, занимая третье место в структуре общей онкологической заболеваемости. Несмотря на все современные диагностические возможности, показатели запущенности неуклонно растут. Доказано, что КРР развивается вследствие поэтапного диспластического изменения слизистой толстой кишки, молекулярно- генетических изменений, которые определяют молекулярную биологию опухоли, её свойства, морфологию, прогноз заболевания и ответ на проводимую терапию. Выделяют следующие механизмы опухолевой прогрессии при КРР: хромосомная нестабильность, микросателлитная нестабильность, «метиляторный» фенотип, зубчатый (serrated) путь раз[1]вития аденокарцином. В последние годы перспективным направлением стало использование молекулярных методов диагностики. Это привело к разработке молекулярно- генетической классификации, включающей в себя 4 подтипа КРР, которые отличаются между собой не только по молекулярно- генетическим характеристикам, но и по клиническому течению и ответу на проводимую терапию.

Today, colorectal cancer (CRC) is the third most common cancer and therefore an urgent problem of oncology. Despite all modern diagnostic capabilities, the rates of advanced cases are growing steadily. CRC was proven to be a result of a phased dysplastic change in the colon mucosa, molecular genetic changes that determine the molecular biology of the tumor, its properties, morphology, disease prognosis and response to therapy. The following mechanisms of CRC tumor progression are distinguished: chromosomal instability, microsatellite instability, "methylator" phenotype, and serrated pathway of adenocarcinoma development. Application of molecular and diagnostic methods has become a promising direction in recent years. This led to the development of a molecular genetic classifi cation with 4 CRC subtypes differing not only in their molecular genetic characteristics, but also in clinical course and response to therapy.

колоректальный ракмолекулярная биологиямолекулярно-генетические подтипыпаттерн-распознающие рецепторытолл-подобные рецепторылимфогенное метастазированиехирургическое лечениеcolorectal cancermolecular biologymolecular and genetic subtypespattern-recognition receptorsToll-like receptorslymphogenous metastasissurgical treatment.ReferencesThe editional board of the cancer statistics in Japan. Cancer statistics in Japan. 2015, 129 с. Доступно по: https:// ganjoho.jp/data/reg_stat/statistics/brochure/2015/cancer_ statistics_2015.pdf. Дата обращения: 15.01.2021.The editional board of the cancer statistics in Japan. Cancer statistics in Japan. 2015. 129 p. Available at: https:// ganjoho.jp/data/reg_stat/statistics/brochure/2015/cancer_ statistics_2015.pdf. Accessed: 15.01.2021.Al-Hajeili M, Shields AF, Hwang JJ, Wadlow RC, Marshall JL. Molecular Testing to Optimize and Personalize Decision Making in the Management of Colorectal Cancer. Oncology (Williston Park). 2017 Apr 15;31(4):301–312.Al-Hajeili M, Shields AF, Hwang JJ, Wadlow RC, Marshall JL. Molecular Testing to Optimize and Personalize Decision Making in the Management of Colorectal Cancer. Oncology (Williston Park). 2017 Apr 15;31(4):301–312.Sepulveda AR, Hamilton SR, Allegra CJ, Grody W, Cushman-Vokoun AM, Funkhouser WK, et al. Molecular Biomarkers for the Evaluation of Colorectal Cancer: Guideline From the American Society for Clinical Pathology, College of American Pathologists, Association for Molecular Pathology, and American Society of Clinical Oncology. J Mol Diagn. 2017 Mar;19(2):187–225. https://doi.org/10.1016/j.jmoldx.2016.11.001Sepulveda AR, Hamilton SR, Allegra CJ, Grody W, Cushman-Vokoun AM, Funkhouser WK, et al. Molecular Biomarkers for the Evaluation of Colorectal Cancer: Guideline From the American Society for Clinical Pathology, College of American Pathologists, Association for Molecular Pathology, and American Society of Clinical Oncology. J Mol Diagn. 2017 Mar;19(2):187–225. https://doi.org/10.1016/j.jmoldx.2016.11.001Muller MF, Ibrahim AEK, Arends MJ. Molecular pathological classification of colorectal cancer. Virchows Arch. 2016 Aug;469(2):125–134. https://doi.org/10.1007/s00428-016-1956-3Muller MF, Ibrahim AEK, Arends MJ. Molecular pathological classification of colorectal cancer. Virchows Arch. 2016 Aug;469(2):125–134. https://doi.org/10.1007/s00428-016-1956-3Bosman F, Yan P. Molecular pathology of colorectal cancer. Pol J Pathol. 2014 Dec;65(4):257–266. https://doi.org/10.5114/pjp.2014.48094Bosman F, Yan P. Molecular pathology of colorectal cancer. Pol J Pathol. 2014 Dec;65(4):257–266. https://doi.org/10.5114/pjp.2014.48094Setaffy L, Langner C. Microsatellite instability in colorectal cancer: clinicopathological signifi cance. Pol J Pathol. 2015 Sep;66(3):203–218. https://doi.org/10.5114/pjp.2015.54953Setaffy L, Langner C. Microsatellite instability in colorectal cancer: clinicopathological signifi cance. Pol J Pathol. 2015 Sep;66(3):203–218. https://doi.org/10.5114/pjp.2015.54953Nazemalhosseini Mojarad E, Kuppen PJ, Aghdaei HA, Zali MR. The CpG island methylator phenotype (CIMP) in colorectal cancer. Gastroenterol Hepatol Bed Bench. 2013;6(3):120–128.Nazemalhosseini Mojarad E, Kuppen PJ, Aghdaei HA, Zali MR. The CpG island methylator phenotype (CIMP) in colorectal cancer. Gastroenterol Hepatol Bed Bench. 2013;6(3):120–128.Rhee Y-Y, Kim K-J, Kang GH. CpG Island Methylator Phenotype-High Colorectal Cancers and Their Prognostic Implications and Relationships with the Serrated Neoplasia Pathway. Gut Liver. 2017 Jan 15;11(1):38–46. https://doi.org/10.5009/gnl15535Rhee Y-Y, Kim K-J, Kang GH. CpG Island Methylator Phenotype-High Colorectal Cancers and Their Prognostic Implications and Relationships with the Serrated Neoplasia Pathway. Gut Liver. 2017 Jan 15;11(1):38–46. https://doi.org/10.5009/gnl15535Агейкина Н.В., Дуванский В.А., Князев М.В., Мальков П.Г., Данилова Н.В., Харлова О.А. Альтернативный путь развития колоректального рака. Гистогенетические и молекулярные особенности зубчатых поражений. Экспериментальная и клиническая гастроэнтерология. 2014:(7(107)):4–12.Ageykina NV, Duvansky VA, Knyazev MV, Malkov PG, Danilova NV, Harlova OA. The alternative way of colorectal cancer developing. the histogenetic and molecular features of serrated lesions. Experimental and Clinical Gastroenterology. 2014:(7(107)):4–12. (In Russian).Мозеров С.А., Комин Ю.А., Новиков Н.Ю., Южаков В.В., Пашкин С.Б., Мозерова Е.С. Опухолевый ответ на неоадьювантную терапию при колоректальном раке. Журнал научных статей здоровье и образование в XXI веке. 2018:20(4):99–108. http://doi.org/10.26787/nydha-2226-7425-2018-20-4-99-108Mozerov SA, Komin YuA, Novikov NYu, Yuzhakov VV, Pashkin SB, Mozerova ES. Tumor response to neoadjuvant therapy in colorectal cancer. Journal of scientifi c articles health and education in the XXI century. 2018:20(4):99–108. http://doi.org/10.26787/nydha-2226-7425-2018-20-4-99-108Muller MF, Ibrahim AEK, Arends MJ. Molecular pathological classification of colorectal cancer. Virchows Arch. 2016 Aug;469(2):125–134. https://doi.org/10.1007/s00428-016-1956-3Muller MF, Ibrahim AEK, Arends MJ. Molecular pathological classifi cation of colorectal cancer. Virchows Arch. 2016 Aug;469(2):125–134. https://doi.org/10.1007/s00428-016-1956-3Budinska E, Popovici V, Tejpar S, D’Ario G, Lapique N, Sikora KO, et al. Gene expression patterns unveil a new level of molecular heterogeneity in colorectal cancer. J Pathol. 2013 Sep;231(1):63–76. https://doi.org/10.1002/path.4212Budinska E, Popovici V, Tejpar S, D’Ario G, Lapique N, Sikora KO, et al. Gene expression patterns unveil a new level of molecular heterogeneity in colorectal cancer. J Pathol. 2013 Sep;231(1):63–76. https://doi.org/10.1002/path.4212Guinney J, Dienstmann R, Wang X, de Reyniès A, Schlicker A, Soneson C, et al. The consensus molecular subtypes of colorectal cancer. Nat Med. 2015 Nov;21(11):1350–1356. https://doi.org/10.1038/nm.3967Guinney J, Dienstmann R, Wang X, de Reyniès A, Schlicker A, Soneson C, et al. The consensus molecular subtypes of colorectal cancer. Nat Med. 2015 Nov;21(11):1350–1356. https://doi.org/10.1038/nm.3967Thanki K, Nicholls ME, Gajjar A, Senagore AJ, Qiu S, Szabo C, et al. Consensus Molecular Subtypes of Colorectal Cancer and their Clinical Implications. Int Biol Biomed J. 2017;3(3):105–111.Thanki K, Nicholls ME, Gajjar A, Senagore AJ, Qiu S, Szabo C, et al. Consensus Molecular Subtypes of Colorectal Cancer and their Clinical Implications. Int Biol Biomed J. 2017;3(3):105–111.Dienstmann R, Vermeulen L, Guinney J, Kopetz S, Tejpar S, Tabernero J. Consensus molecular subtypes and the evolution of precision medicine in colorectal cancer. Nat Rev Cancer. 2017 Feb;17(2):79–92. https://doi.org/10.1038/nrc.2016.126Dienstmann R, Vermeulen L, Guinney J, Kopetz S, Tejpar S, Tabernero J. Consensus molecular subtypes and the evolution of precision medicine in colorectal cancer. Nat Rev Cancer. 2017 Feb;17(2):79–92. https://doi.org/10.1038/nrc.2016.126Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011 Mar 4;144(5):646–674. https://doi.org/10.1016/j.cell.2011.02.013Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011 Mar 4;144(5):646–674. https://doi.org/10.1016/j.cell.2011.02.013Zhao Y, Butler EB, Tan M. Targeting cellular metabolism to improve cancer therapeutics. Cell Death Dis. 2013 Mar 7;4:e532. https://doi.org/10.1038/cddis.2013.60Zhao Y, Butler EB, Tan M. Targeting cellular metabolism to improve cancer therapeutics. Cell Death Dis. 2013 Mar 7;4:e532. https://doi.org/10.1038/cddis.2013.60Sadanandam A, Lyssiotis CA, Homicsko K, Collisson EA, Gibb WJ, Wullschleger S, et al. A colorectal cancer classifi cation system that associates cellular phenotype and responses to therapy. Nat Med. 2013 May;19(5):619–625. https://doi.org/10.1038/nm.3175Sadanandam A, Lyssiotis CA, Homicsko K, Collisson EA, Gibb WJ, Wullschleger S, et al. A colorectal cancer classifi cation system that associates cellular phenotype and responses to therapy. Nat Med. 2013 May;19(5):619–625. https://doi.org/10.1038/nm.3175Okita A, Takahashi S, Ouchi K, Inoue M, Watanabe M, Endo M, et al. Consensus molecular subtypes classifi cation of colorectal cancer as a predictive factor for chemotherapeutic efficacy against metastatic colorectal cancer. Oncotarget. 2018 Apr 10;9(27):18698–18711. https://doi.org/10.18632/oncotarget.24617Okita A, Takahashi S, Ouchi K, Inoue M, Watanabe M, Endo M, et al. Consensus molecular subtypes classifi cation of colorectal cancer as a predictive factor for chemotherapeutic effi cacy against metastatic colorectal cancer. Oncotarget. 2018 Apr 10;9(27):18698–18711. https://doi.org/10.18632/oncotarget.24617Fontana E, Nyamundanda G, Cunningham D, Ragulan C, Sclafani F, Eason K, et al. Molecular subtype assay to reveal anti-EGFR response sub-clones in colorectal cancer (CRC). JCO. 2018 Feb 1;36(4_suppl):658–658. https://doi.org/10.1200/jco.2018.36.4_suppl.658Fontana E, Nyamundanda G, Cunningham D, Ragulan C, Sclafani F, Eason K, et al. Molecular subtype assay to reveal anti-EGFR response sub-clones in colorectal cancer (CRC). JCO. 2018 Feb 1;36(4_suppl):658–658. https://doi.org/10.1200/jco.2018.36.4_suppl.658Tejpar S, Stintzing S, Ciardiello F, Tabernero J, Van Cutsem E, Beier F, et al. Prognostic and Predictive Relevance of Primary Tumor Location in Patients with RAS Wild-Type Metastatic Colorectal Cancer: Retrospective Analyses of the CRYSTAL and FIRE-3 Trials. JAMA Oncol. 2017 Feb 1;3(2):194–201. https://doi.org/10.1001/jamaoncol.2016.3797Tejpar S, Stintzing S, Ciardiello F, Tabernero J, Van CutsemE, Beier F, et al. Prognostic and Predictive Relevance of Primary Tumor Location in Patients with RAS Wild-Type Metastatic Colorectal Cancer: Retrospective Analyses of the CRYSTAL 56 and FIRE-3 Trials. JAMA Oncol. 2017 Feb 1;3(2):194–201. https://doi.org/10.1001/jamaoncol.2016.3797Venook AP, Ou F-S, Lenz H-J, Kabbarah O, Qu X, Niedzwiecki D, et al. Primary (1°) tumor location as an independent prognostic marker from molecular features for overall survival (OS) in patients (pts) with metastatic colorectal cancer (mCRC): Analysis of CALGB / SWOG 80405 (Alliance). JCO. 2017 May 20;35(15_suppl):3503–3503. https://doi.org/10.1200/jco.2017.35.15_suppl.3503Venook AP, Ou F-S, Lenz H-J, Kabbarah O, Qu X, Niedzwiecki D, et al. Primary (1°) tumor location as an independent prognostic marker from molecular features for overall survival (OS) in patients (pts) with metastatic colorectal cancer (mCRC): Analysis of CALGB / SWOG 80405 (Alliance). JCO. 2017 May 20;35(15_suppl):3503–3503. https://doi.org/10.1200/jco.2017.35.15_suppl.3503Sagawa T, Hamaguchi K, Sakurada A, Tamura F, Hayashi T, Fujikawa K, et al. Primary tumor location as a prognostic and predictive factor in metastatic colorectal cancer (mCRC) treated with chemotherapy plus cetuximab: A retrospective analysis. JCO. 2017 Feb 1;35(4_suppl):711–711. https://doi.org/10.1200/jco.2017.35.4_suppl.711Sagawa T, Hamaguchi K, Sakurada A, Tamura F, Hayashi T, Fujikawa K, et al. Primary tumor location as a prognostic and predictive factor in metastatic colorectal cancer (mCRC) treated with chemotherapy plus cetuximab: A retrospective analysis. JCO. 2017 Feb 1;35(4_suppl):711–711. https://doi.org/10.1200/jco.2017.35.4_suppl.711Stintzing S, Wirapati P, Lenz H-J, Neureiter D, Fischer von Weikersthal L, Decker T, et al. Consensus molecular subgroups (CMS) of colorectal cancer (CRC) and fi rst-line effi cacy of FOLFIRI plus cetuximab or bevacizumab in the FIRE3 (AIO KRK-0306) trial. JCO. 2017 May 20;35(15_suppl):3510–3510. https://doi.org/10.1200/jco.2017.35.15_suppl.3510Stintzing S, Wirapati P, Lenz H-J, Neureiter D, Fischer von Weikersthal L, Decker T, et al. Consensus molecular subgroups (CMS) of colorectal cancer (CRC) and fi rst-line effi cacy of FOLFIRI plus cetuximab or bevacizumab in the FIRE3 (AIO KRK-0306) trial. JCO. 2017 May 20;35(15_suppl):3510–3510. https://doi.org/10.1200/jco.2017.35.15_suppl.3510Boland PM, Ma WW. Immunotherapy for Colorectal Cancer. Cancers (Basel). 2017 May 11;9(5). https://doi.org/10.3390/cancers9050050Boland PM, Ma WW. Immunotherapy for Colorectal Cancer. Cancers (Basel). 2017 May 11;9(5). https://doi.org/10.3390/cancers9050050

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