medgenМедицинская генетикаMedical Genetics2073-7998Publishing House «Genius Media» LLC10.25557/2073-7998.2025.05.5-15medgen-2959Research ArticleНАУЧНЫЕ ОБЗОРЫREVIEWМутации гена RET и их значение в таргетной терапии медуллярного рака щитовидной железыRET gene mutations and their importance in targeted therapy of medullary thyroid cancerКимН.KimN.

Наталья Ким 

197022, г. Санкт-Петербург, ул. Льва Толстого, д. 6-8 

Natalya Kim 

6-8, L’va Tolstogo st., Saint Petersburg, 197022, Russian Federation 

kim.nat.official@gmail.comБудаеваА. А.BudaevaA. A.

197022, г. Санкт-Петербург, ул. Льва Толстого, д. 6-8 

6-8, L’va Tolstogo st., Saint Petersburg, 197022, Russian Federation 

ЗахаровВ. В.ZakharovV. V.

197022, г. Санкт-Петербург, ул. Льва Толстого, д. 6-8 

6-8, L’va Tolstogo st., Saint Petersburg, 197022, Russian Federation 

ШуиповаС. У.ShuipovaS. U.

355017, г. Ставрополь, ул. Мира, д. 310

310, Mira st., Stavropol, 355017, Russian Federation 

ДишнаевЮ. Р.DishnaevI. R.

450008, г. Уфа, ул. Ленина, д. 3 

3, Lenina st., Ufa, 450008, Russian Federation 

МеджидовЭ. А.MedzhidovE. A.

450008, г. Уфа, ул. Ленина, д. 3

3, Lenina st., Ufa, 450008, Russian Federation 

ЗахаренкоА. А.ZakharenkoA. A.

197022, г. Санкт-Петербург, ул. Льва Толстого, д. 6-8 

6-8, L’va Tolstogo st., Saint Petersburg, 197022, Russian Federation 

БорисковаМ. Е.BoriskovaM. E.

197022, г. Санкт-Петербург, ул. Льва Толстого, д. 6-8 

6-8, L’va Tolstogo st., Saint Petersburg, 197022, Russian Federation 

НазаровВ. Д.NazarovV. D.

197022, г. Санкт-Петербург, ул. Льва Толстого, д. 6-8 

6-8, L’va Tolstogo st., Saint Petersburg, 197022, Russian Federation 

ОмаровМ. А.OmarovM. A.

197022, г. Санкт-Петербург, ул. Льва Толстого, д. 6-8 

6-8, L’va Tolstogo st., Saint Petersburg, 197022, Russian Federation 

ФГБОУ ВО Первый Санкт-Петербургский государственный медицинский университет имени академика И.П. Павлова Минздрава РоссииРоссияPavlov First Saint Petersburg State Medical UniversityRussian FederationФГБОУ ВО Ставропольский государственный медицинский университет Минздрава РоссииРоссияStavropol State Medical UniversityRussian FederationФГБОУ ВО Башкирский государственный медицинский университет Минздрава РоссииРоссияBashkir State Medical UniversityRussian Federation202530072025245515Copyright © Ким Н., Будаева А.А., Захаров В.В., Шуипова С.У., Дишнаев Ю.Р., Меджидов Э.А., Захаренко А.А., Борискова М.Е., Назаров В.Д., Омаров М.А., 20252025Ким Н., Будаева А.А., Захаров В.В., Шуипова С.У., Дишнаев Ю.Р., Меджидов Э.А., Захаренко А.А., Борискова М.Е., Назаров В.Д., Омаров М.А.Kim N., Budaeva A.A., Zakharov V.V., Shuipova S.U., Dishnaev I.R., Medzhidov E.A., Zakharenko A.A., Boriskova M.E., Nazarov V.D., Omarov M.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.medgen-journal.ru/jour/article/view/2959

Медуллярный рак щитовидной железы (МРЩЖ) - относительно редкая (около 2–5% всех случаев рака щитовидной железы) форма злокачественной опухоли, характеризующаяся агрессивным клиническим течением. Ключевую роль в патогенезе играют активирующие мутации протоонкогена RET (REarranged during Transfection, RET), обнаруживаемые во всех наследственных случаях и примерно у половины спорадических МРЩЖ; эти генетические изменения служат важными мишенями для таргетной терапии. Цель данного обзора – обобщить современные данные о спектре мутаций гена RET при МРЩЖ и оценить их значение для таргетной терапии. В обзоре описаны наиболее распространённые мутации RET (например, точечные замены p.Met918Thr и p.Cys634Arg), а также химерные перестройки этого гена, и обсуждается их связь с чувствительностью опухоли к таргетным препаратам. Рассматриваются подходы к выбору терапии в зависимости от молекулярного профиля опухоли, включая применение ингибиторов тирозинкиназы RET первого поколения (мультикиназные ингибиторы, например, вандетаниб и кабозантиниб) и высокоселективных ингибиторов RET второго поколения (например, селперкатиниб и пралсретиниб). Отдельное внимание уделено роли молекулярно-генетического тестирования гена RET в оптимизации лечения МРЩЖ. В заключение подчёркивается необходимость персонализированного подхода и молекулярной стратификации пациентов с МРЩЖ, а также отмечаются перспективы внедрения новых таргетных препаратов, нацеленных на различные мутации RET.

Medullary thyroid carcinoma (MTC) is a relatively rare malignancy (approximately 2–5% of all thyroid cancers) characterized by an aggressive clinical course. Activating mutations of the RET (REarranged during Transfection) proto-oncogene play a key role in MTC pathogenesis, being present in all hereditary cases and about half of sporadic cases, and these genetic alterations represent critical targets for targeted therapy. This review summarizes current data on the spectrum of RET gene mutations in MTC and evaluates their significance for targeted therapy. The most common RET mutations (such as point mutations p.Met918Thr and p.Cys634Arg) as well as chimeric rearrangements (fusions) of the RET gene are described, and their association with tumor sensitivity to targeted therapies is discussed. Approaches to therapy selection based on the tumor’s molecular profile are considered, including the use of first-generation RET tyrosine kinase inhibitors (multi-kinase agents, e.g., vandetanib and cabozantinib) and highly selective second-generation RET inhibitors (e.g., selpercatinib and pralsetinib). Special attention is given to the role of molecular genetic testing of RET in optimizing MTC treatment. In conclusion, the need for a personalized approach with molecular stratification of MTC patients by RET status is emphasized, and the promise of new targeted agents directed at various RET mutations is highlighted.

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