nogrЭкспериментальная и клиническая гастроэнтерологияExperimental and Clinical Gastroenterology1682-8658«Global Media Technologies»10.31146/1682-8658-ecg-205-9-222-228nogr-2061Research ArticleОБЗОРREVIEWТаргетная терапия в онкологииTargeted therapy in oncologyhttps://orcid.org/0000-0002-3786-9995СеменкинАлександр АнатольевичSemenkinA. A.noemail@neicon.ruhttps://orcid.org/0000-0002-4462-569XСапроненкоВладимир СергеевичSapronenkoV. S.vssapronenko@mail.ruhttps://orcid.org/0000-0002-0601-7044ЛогиноваЕкатерина НиколаевнаLoginovaE. N.noemail@neicon.ruhttps://orcid.org/0000-0003-0440-7118НадейЕлена ВитальевнаNadeyE. V.noemail@neicon.ruФедеральное государственное бюджетное образовательное учреждение высшего образования «Омский государственный медицинский университет» Министерства здравоохранения Российской ФедерацииРоссияOmsk State Medical UniversityRussian Federation20220710202209222228Copyright © Семенкин А.А., Сапроненко В.С., Логинова Е.Н., Надей Е.В., 20222022Семенкин А.А., Сапроненко В.С., Логинова Е.Н., Надей Е.В.Semenkin A.A., Sapronenko V.S., Loginova E.N., Nadey E.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.nogr.org/jour/article/view/2061

Цель обзора - осветить принцип действия, эффективность и перспективы развития таргетной терапии в лечении пациентов со злокачественными новообразованиями на основании последних клинических исследований. Благодаря активному изучению биологии опухолей были обнаружены специфические молекулы-мишени и стало возможным точечное воздействие на опухолевые клетки при помощи таргетных препаратов. На сегодняшний день таргетные препараты применяются в лечении злокачественных опухолей различных органов и продолжают демонстрировать свою эффективность, увеличивая общую выживаемость и время без прогрессирования, по сравнению с прежними стандартами лечения

The aim of the review is to highlight the principle of action, effectiveness and prospects for the development of targeted therapy in the treatment of patients with malignant neoplasms based on recent clinical studies. Thanks to the active study of tumor biology, specific target molecules have been discovered and it has become possible to target tumor cells with targeted drugs. Today, targeted drugs are used in the treatment of malignant tumors of various organs and continue to demonstrate their effectiveness, improve overall survival and progression-free time, compared with previous standards of treatment.

таргетная терапияракзлокачественные новообразованиявремя без прогрессированияперсонализированная онкологияtargeted therapycancermalignant neoplasmsprogression-free timepersonalized oncologyReferencesFerlay J., Ervik M., Lam F., et al. Global Cancer Observatory: Cancer Today. Lyon: International Agency for Research on Cancer; 2020. Available at: https://gco.iarc.fr/today (Accessed: 27 March 2022)Ferlay J., Ervik M., Lam F., et al. Global Cancer Observatory: Cancer Today. Lyon: International Agency for Research on Cancer; 2020. Available at: https://gco.iarc.fr/today (Accessed: 27 March 2022)Smelov P. A., Nikitina S.YU. (red) Healthcare in Russia. 2021. Moscow. Stat.sb./Rosstat Publ., 2021. (In Russ.) @@Смелов П. А., Никитина С. Ю. (ред) Здравоохранение в России. 2021. - Москва: Стат.сб./Росстат, 2021.Smelov P. A., Nikitina S.YU. (red) Healthcare in Russia. 2021. Moscow. Stat.sb./Rosstat Publ., 2021. (In Russ.) @@Смелов П. А., Никитина С. Ю. (ред) Здравоохранение в России. 2021. - Москва: Стат.сб./Росстат, 2021.Hanahan D., Weinberg R. A. The hallmarks of cancer. Cell. 2000;100(1):57-70. doi:10.1016/s0092-8674(00)81683-9Hanahan D., Weinberg R. A. The hallmarks of cancer. Cell. 2000;100(1):57-70. doi:10.1016/s0092-8674(00)81683-9Hanahan D., Weinberg R. A. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646-674. doi:10.1016/j.cell.2011.02.013Hanahan D., Weinberg R. A. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646-674. doi:10.1016/j.cell.2011.02.013Tyulyandin S. A. Targeted therapy: Twenty years of success and failures. Practical oncology. 2019;4(20):274-288. (In Russ.) doi:10.31917/2004274 @@Тюляндин С. А. Таргетная терапия: двадцать лет успехов и поражений. Практическая онкология. 2019;4(20):274-288. doi:10.31917/2004274Tyulyandin S. A. Targeted therapy: Twenty years of success and failures. Practical oncology. 2019;4(20):274-288. (In Russ.) doi:10.31917/2004274 @@Тюляндин С. А. Таргетная терапия: двадцать лет успехов и поражений. Практическая онкология. 2019;4(20):274-288. doi:10.31917/2004274Druker B. J., Talpaz M., Resta D. J., et al. Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. The New England Journal of Medicine. 2001;344(14):1031-1037. doi:10.1056/NEJM200104053441401Druker B. J., Talpaz M., Resta D. J., et al. Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. The New England Journal of Medicine. 2001;344(14):1031-1037. doi:10.1056/NEJM200104053441401Lynch T. J., Bell D. W., Sordella R., et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. The New England Journal of Medicine. 2004;350(21):2129-2139. doi:10.1056/NEJMoa040938Lynch T. J., Bell D. W., Sordella R., et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. The New England Journal of Medicine. 2004;350(21):2129-2139. doi:10.1056/NEJMoa040938Escudier B., Worden F., Kudo M. Sorafenib: key lessons from over 10 years of experience. Expert Review of Anticancer Therapy. 2019;19(2):177-189. doi:10.1080/14737140.2019.1559058Escudier B., Worden F., Kudo M. Sorafenib: key lessons from over 10 years of experience. Expert Review of Anticancer Therapy. 2019;19(2):177-189. doi:10.1080/14737140.2019.1559058Cabanillas M. E., Takahashi S. Managing the adverse events associated with lenvatinib therapy in radioiodine-refractory differentiated thyroid cancer. Seminars in Oncology. 2019;46(1):57-64. doi:10.1053/j.seminoncol.2018.11.004Cabanillas M. E., Takahashi S. Managing the adverse events associated with lenvatinib therapy in radioiodine-refractory differentiated thyroid cancer. Seminars in Oncology. 2019;46(1):57-64. doi:10.1053/j.seminoncol.2018.11.004Cabanillas M. E., Ryder M., Jimenez C. Targeted Therapy for Advanced Thyroid Cancer: Kinase Inhibitors and Beyond. Endocrine Reviews. 2019;40(6):1573-1604. doi:10.1210/er.2019-00007Cabanillas M. E., Ryder M., Jimenez C. Targeted Therapy for Advanced Thyroid Cancer: Kinase Inhibitors and Beyond. Endocrine Reviews. 2019;40(6):1573-1604. doi:10.1210/er.2019-00007Ramos H. E., Hecht F., Berdelou A., et al. Long-term follow-up and safety of vandetanib for advanced medullary thyroid cancer. Endocrine Journal. 2021;71(2):434-442. doi:10.1007/s12020-020-02426-xRamos H. E., Hecht F., Berdelou A., et al. Long-term follow-up and safety of vandetanib for advanced medullary thyroid cancer. Endocrine Journal. 2021;71(2):434-442. doi:10.1007/s12020-020-02426-xKaprin A. D., Ivanov S. A., Sevryukov F. E., et al. Efficacy of external beam radiotherapy and targeted therapy with vandenanib in patients with inoperable and progressive medullary thyroid cancer. Head and neck tumors. 2018;8(3):72-76. (In Russ.) doi:10.17650/2222-1468-2018-8-3-72-76 @@Каприн А. Д., Иванов С. А., Севрюков Ф. Е. и соавт. Эффективность дистанционной лучевой терапии и таргетной терапии вандетанибом нерезектабельного и прогрессирующего медуллярного рака щитовидной железы. Опухоли головы и шеи. 2018;8(3):72-76. doi:10.17650/2222-1468-2018-8-3-72-76Kaprin A. D., Ivanov S. A., Sevryukov F. E., et al. Efficacy of external beam radiotherapy and targeted therapy with vandenanib in patients with inoperable and progressive medullary thyroid cancer. Head and neck tumors. 2018;8(3):72-76. (In Russ.) doi:10.17650/2222-1468-2018-8-3-72-76 @@Каприн А. Д., Иванов С. А., Севрюков Ф. Е. и соавт. Эффективность дистанционной лучевой терапии и таргетной терапии вандетанибом нерезектабельного и прогрессирующего медуллярного рака щитовидной железы. Опухоли головы и шеи. 2018;8(3):72-76. doi:10.17650/2222-1468-2018-8-3-72-76Kornblum N., Zhao F., Manola J., et al. Randomized Phase II Trial of Fulvestrant Plus Everolimus or Placebo in Postmenopausal Women With Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer Resistant to Aromatase Inhibitor Therapy: Results of PrE0102. Journal of Clinical Oncology. 2018;36(16):1556-1563. doi:10.1200/JCO.2017.76.9331Kornblum N., Zhao F., Manola J., et al. Randomized Phase II Trial of Fulvestrant Plus Everolimus or Placebo in Postmenopausal Women With Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer Resistant to Aromatase Inhibitor Therapy: Results of PrE0102. Journal of Clinical Oncology. 2018;36(16):1556-1563. doi:10.1200/JCO.2017.76.9331André F., Ciruelos E., Rubovszky G., et al. SOLAR-1 Study Group. Alpelisib for PIK3CA-Mutated, Hormone Receptor-Positive Advanced Breast Cancer. The New England Journal of Medicine. 2019;380(20):1929-1940. doi:10.1056/NEJMoa1813904André F., Ciruelos E., Rubovszky G., et al. SOLAR-1 Study Group. Alpelisib for PIK3CA-Mutated, Hormone Receptor-Positive Advanced Breast Cancer. The New England Journal of Medicine. 2019;380(20):1929-1940. doi:10.1056/NEJMoa1813904Genuino A. J., Chaikledkaew U., The D. O., et al. Adjuvant trastuzumab regimen for HER2-positive early-stage breast cancer: a systematic review and meta-analysis. Expert Review of Clinical Pharmacology. 2019;12(8):815-824. doi:17512433.2019.1637252Genuino A. J., Chaikledkaew U., The D. O., et al. Adjuvant trastuzumab regimen for HER2-positive early-stage breast cancer: a systematic review and meta-analysis. Expert Review of Clinical Pharmacology. 2019;12(8):815-824. doi:17512433.2019.1637252Cameron D., Piccart-Gebhart M.J., Gelber R. D., et al. Herceptin Adjuvant (HERA) Trial Study Team. 11 years’ follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive early breast cancer: final analysis of the HERceptin Adjuvant (HERA) trial. The Lancet. 2017;389(10075):1195-1205. doi:10.1016/S0140-6736(16)32616-2Cameron D., Piccart-Gebhart M.J., Gelber R. D., et al. Herceptin Adjuvant (HERA) Trial Study Team. 11 years’ follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive early breast cancer: final analysis of the HERceptin Adjuvant (HERA) trial. The Lancet. 2017;389(10075):1195-1205. doi:10.1016/S0140-6736(16)32616-2Mok T., Yang J. J., Lam K. C. Treating patients with EGFR-sensitizing mutations: first line or second line - is there a difference? Journal of Clinical Oncology. 2013;31(8):1081-1088. doi:10.1200/JCO.2012.43.0652Mok T., Yang J. J., Lam K. C. Treating patients with EGFR-sensitizing mutations: first line or second line - is there a difference? Journal of Clinical Oncology. 2013;31(8):1081-1088. doi:10.1200/JCO.2012.43.0652Hosomi Y., Morita S., Sugawara S., et al. North-East Japan Study Group. Gefitinib Alone Versus Gefitinib Plus Chemotherapy for Non-Small-Cell Lung Cancer With Mutated Epidermal Growth Factor Receptor: NEJ009 Study. Journal of Clinical Oncology. 2020;38(2):115-123. doi:10.1200/JCO.19.01488Hosomi Y., Morita S., Sugawara S., et al. North-East Japan Study Group. Gefitinib Alone Versus Gefitinib Plus Chemotherapy for Non-Small-Cell Lung Cancer With Mutated Epidermal Growth Factor Receptor: NEJ009 Study. Journal of Clinical Oncology. 2020;38(2):115-123. doi:10.1200/JCO.19.01488Remon J., Steuer C. E., Ramalingam S. S., et al. Osimertinib and other third-generation EGFR TKI in EGFR-mutant NSCLC patients. Annals of Oncology. 2018;29:20-27. doi:10.1093/annonc/mdx704Remon J., Steuer C. E., Ramalingam S. S., et al. Osimertinib and other third-generation EGFR TKI in EGFR-mutant NSCLC patients. Annals of Oncology. 2018;29:20-27. doi:10.1093/annonc/mdx704Solomon B. J., Mok T., Kim D. W., et al. PROFILE 1014 Investigators. First-line crizotinib versus chemotherapy in ALK-positive lung cancer. The New England Journal of Medicine. 2014;371(23):2167-2177. doi:10.1056/NEJMoa1408440Solomon B. J., Mok T., Kim D. W., et al. PROFILE 1014 Investigators. First-line crizotinib versus chemotherapy in ALK-positive lung cancer. The New England Journal of Medicine. 2014;371(23):2167-2177. doi:10.1056/NEJMoa1408440Peters S., Camidge D. R., Shaw A. T., et al. ALEX Trial Investigators. Alectinib versus Crizotinib in Untreated ALK-Positive Non-Small-Cell Lung Cancer. The New England Journal of Medicine. 2017;377(9):829-838. doi:10.1056/NEJMoa1704795Peters S., Camidge D. R., Shaw A. T., et al. ALEX Trial Investigators. Alectinib versus Crizotinib in Untreated ALK-Positive Non-Small-Cell Lung Cancer. The New England Journal of Medicine. 2017;377(9):829-838. doi:10.1056/NEJMoa1704795Shaw A. T., Riely G. J., Bang Y. J., et al. Crizotinib in ROS1-rearranged advanced non-small-cell lung cancer (NSCLC): updated results, including overall survival, from PROFILE 1001. Annals of Oncology. 2019;30(7):1121-1126. doi:10.1093/annonc/mdz131Shaw A. T., Riely G. J., Bang Y. J., et al. Crizotinib in ROS1-rearranged advanced non-small-cell lung cancer (NSCLC): updated results, including overall survival, from PROFILE 1001. Annals of Oncology. 2019;30(7):1121-1126. doi:10.1093/annonc/mdz131Patel T.H, Cecchini M. Targeted Therapies in Advanced Gastric Cancer. Current Treatment Options in Oncology. 2020;21(9):70. doi:10.1007/s11864-020-00774-4Patel T.H, Cecchini M. Targeted Therapies in Advanced Gastric Cancer. Current Treatment Options in Oncology. 2020;21(9):70. doi:10.1007/s11864-020-00774-4Shitara K., Bang Y. J., Iwasa S., et al. DESTINY-Gastric01 Investigators. Trastuzumab Deruxtecan in Previously Treated HER2-Positive Gastric Cancer. The New England Journal of Medicine. 2020;382(25):2419-2430. doi:10.1056/NEJMoa2004413Shitara K., Bang Y. J., Iwasa S., et al. DESTINY-Gastric01 Investigators. Trastuzumab Deruxtecan in Previously Treated HER2-Positive Gastric Cancer. The New England Journal of Medicine. 2020;382(25):2419-2430. doi:10.1056/NEJMoa2004413Kudo M., Ueshima K., Ikeda M., et al. TACTICS study group. Randomised, multicentre prospective trial of transarterial chemoembolisation (TACE) plus sorafenib as compared with TACE alone in patients with hepatocellular carcinoma: TACTICS trial. Gut. 2020;69(8):1492-1501. doi:10.1136/gutjnl-2019-318934Kudo M., Ueshima K., Ikeda M., et al. TACTICS study group. Randomised, multicentre prospective trial of transarterial chemoembolisation (TACE) plus sorafenib as compared with TACE alone in patients with hepatocellular carcinoma: TACTICS trial. Gut. 2020;69(8):1492-1501. doi:10.1136/gutjnl-2019-318934Takeda H., Nishijima N., Nasu A., et al. Long-term antitumor effect of lenvatinib on unresectable hepatocellular carcinoma with portal vein invasion. Hepatology Research. 2019;49(5):594-599. doi:10.1111/hepr.13294Takeda H., Nishijima N., Nasu A., et al. Long-term antitumor effect of lenvatinib on unresectable hepatocellular carcinoma with portal vein invasion. Hepatology Research. 2019;49(5):594-599. doi:10.1111/hepr.13294Kudo M., Ueshima K., Chan S., et al. Lenvatinib as an Initial Treatment in Patients with Intermediate-Stage Hepatocellular Carcinoma Beyond Up-To-Seven Criteria and Child-Pugh A Liver Function: A Proof-Of-Concept Study. Cancers. 2019;11(8):1084. doi:10.3390/cancers11081084Kudo M., Ueshima K., Chan S., et al. Lenvatinib as an Initial Treatment in Patients with Intermediate-Stage Hepatocellular Carcinoma Beyond Up-To-Seven Criteria and Child-Pugh A Liver Function: A Proof-Of-Concept Study. Cancers. 2019;11(8):1084. doi:10.3390/cancers11081084Bruix J., Qin S., Merle P., et al. RESORCE Investigators. Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial. The Lancet. 2017;389(10064):56-66. doi:10.1016/S0140-6736(16)32453-9Bruix J., Qin S., Merle P., et al. RESORCE Investigators. Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial. The Lancet. 2017;389(10064):56-66. doi:10.1016/S0140-6736(16)32453-9Van Cutsem E., Tabernero J., Lakomy R., et al. Addition of aflibercept to fluorouracil, leucovorin, and irinotecan improves survival in a phase III randomized trial in patients with metastatic colorectal cancer previously treated with an oxaliplatin-based regimen. Journal of Clinical Oncology. 2012;30(28):3499-3506. doi:10.1200/JCO.2012.42.8201Van Cutsem E., Tabernero J., Lakomy R., et al. Addition of aflibercept to fluorouracil, leucovorin, and irinotecan improves survival in a phase III randomized trial in patients with metastatic colorectal cancer previously treated with an oxaliplatin-based regimen. Journal of Clinical Oncology. 2012;30(28):3499-3506. doi:10.1200/JCO.2012.42.8201Piawah S., Venook A. P. Targeted therapy for colorectal cancer metastases: A review of current methods of molecularly targeted therapy and the use of tumor biomarkers in the treatment of metastatic colorectal cancer. Cancer. 2019;125(23):4139-4147. doi:10.1002/cncr.32163Piawah S., Venook A. P. Targeted therapy for colorectal cancer metastases: A review of current methods of molecularly targeted therapy and the use of tumor biomarkers in the treatment of metastatic colorectal cancer. Cancer. 2019;125(23):4139-4147. doi:10.1002/cncr.32163Biller L. H., Schrag D. Diagnosis and Treatment of Metastatic Colorectal Cancer: A Review. Journal of the American Medical Association. 2021;325(7):669-685. doi:10.1001/jama.2021.0106Biller L. H., Schrag D. Diagnosis and Treatment of Metastatic Colorectal Cancer: A Review. Journal of the American Medical Association. 2021;325(7):669-685. doi:10.1001/jama.2021.0106Dhillon S. Regorafenib: A Review in Metastatic Colorectal Cancer. Drugs. 2018;78(11):1133-1144. doi:10.1007/s40265-018-0938-yDhillon S. Regorafenib: A Review in Metastatic Colorectal Cancer. Drugs. 2018;78(11):1133-1144. doi:10.1007/s40265-018-0938-yChapman P. B., Hauschild A., Robert C., et al. BRIM-3 Study Group. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. The New England Journal of Medicine. 2011;364(26):2507-2516. doi:10.1056/NEJMoa1103782Chapman P. B., Hauschild A., Robert C., et al. BRIM-3 Study Group. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. The New England Journal of Medicine. 2011;364(26):2507-2516. doi:10.1056/NEJMoa1103782Robert C., Grob J. J., Stroyakovskiy D., et al. Five-Year Outcomes with Dabrafenib plus Trametinib in Metastatic Melanoma. The New England Journal of Medicine. 2019;381(7):626-636. doi:10.1056/NEJMoa1904059Robert C., Grob J. J., Stroyakovskiy D., et al. Five-Year Outcomes with Dabrafenib plus Trametinib in Metastatic Melanoma. The New England Journal of Medicine. 2019;381(7):626-636. doi:10.1056/NEJMoa1904059Sun J., Carr M. J., Khushalani N. I. Principles of Targeted Therapy for Melanoma. Surgical Clinics of North America. 2020;100(1):175-188. doi:10.1016/j.suc.2019.09.013Sun J., Carr M. J., Khushalani N. I. Principles of Targeted Therapy for Melanoma. Surgical Clinics of North America. 2020;100(1):175-188. doi:10.1016/j.suc.2019.09.013

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