Head and Neck TumorsHead and Neck TumorsОпухоли головы и шеи2222-14682411-4634Publishing House ABV Press52910.17650/2222-1468-2020-10-2-69-78REVIEWОБЗОРНАЯ СТАТЬЯMammary analogue secretory carcinoma of the salivary gland with NTRK fusions: new approaches for diagnostics and targeted therapy (review)MASC-карцинома околоушной слюнной железы: современные возможности диагностики и таргетной терапии при транслокациях (слияниях) в гене NTRKhttps://orcid.org/0000-0002-6796-0968IgnatovaA. V.ИгнатоваА. В.
Russian Federation

Bld. 1, 2/1 Barrikadnaya St., Moscow 125993

6 Miklukho-Maklaya St., Moscow 117198

Анастасия Валерьевна Игнатова 

125993 Москва, ул. Баррикадная, 2/1, стр. 1

117198 Москва, ул. Миклухо-Маклая, 6

annasurge@gmail.comhttps://orcid.org/0000-0002-0918-3857MudunovA. M.МудуновА. М.
Russian Federation

Bld. 1, 2/1 Barrikadnaya St., Moscow 125993

24 Kashirskoe Shosse, Moscow 115478

125993 Москва, ул. Баррикадная, 2/1, стр. 1

115478 Москва, Каширское шоссе, 24

https://orcid.org/0000-0003-1341-0765PodvyaznikovS. О.ПодвязниковС. О.
Russian Federation

Bld. 1, 2/1 Barrikadnaya St., Moscow 125993

125993 Москва, ул. Баррикадная, 2/1, стр. 1

https://orcid.org/0000-0002-6851-9867AlymovYu. V.АлымовЮ. В.
Russian Federation

24 Kashirskoe Shosse, Moscow 115478

115478 Москва, Каширское шоссе, 24

Russian Medical Academy of Continuing Professional Education, Ministry of Health of RussiaФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования» Минздрава РоссииRUDN UniversityФГАОУ ВО «Российский университет дружбы народов»N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of RussiaФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Блохина» Минздрава России2407202010269782407202024072020Copyright ©; 2020, Ignatova A.V., Mudunov A.M., Podvyaznikov S.О., Alymov Y.V.Copyright ©; 2020, Игнатова А.В., Мудунов А.М., Подвязников С.О., Алымов Ю.В.2020Ignatova A.V., Mudunov A.M., Podvyaznikov S.О., Alymov Y.V.Игнатова А.В., Мудунов А.М., Подвязников С.О., Алымов Ю.В.https://creativecommons.org/licenses/by/4.0https://ogsh.abvpress.ru/jour/article/view/529

Mammary analogue secretory carcinoma (MASC) of the salivary gland is a rare salivary cancer, histologically resembling to secretory carcinoma of the breast. In 2017 World Health Organization reported MASC is a new salivary cancer subtype. The aim of this article is to collect and analyze data about MASC, particularly clinical, histological and molecular profile, to evaluate targeted therapy effects. We discuss a case report of dramatic and durable response with entrectinib and the development of acquired resistance in an NTRK3-fusion positive salivary cancer, detected by next-generation sequencing. Next-generation sequencing as a comprehensive molecular profiling, that helps to investigate molecular profile of rare tumors and gives an opportunity to use an effective therapeutic options. Identifying ETV6-NTRK3 positive MASC provides a better prognosis for metastatic disease by using a novel effective targeted therapy with tyrosine kinase inhibitors (entrectinib, larotrectinib). Despite a durable and dramatic response, we showed an interesting case of the development of acquired resistance to tyrosine kinase inhibitors mediated by the appearance of a novel NTRK3 G623R mutation. Finally, we believe in great perspectives of comprehensive molecular profiling and targeted therapy for rare malignancies with NTRK gene fusions, including second-generation tyrosine kinase inhibitors.

MASC-карцинома слюнной железы, аналог секреторной карциномы молочной железы (mammary analogue secretory carcinoma) – редкая злокачественная опухоль слюнной железы, которая по гистологическому строению похожа на секреторную карциному молочной железы. В 2017 г. Всемирная организация здравоохранения выделила эти опухоли в отдельный подтип в гистологической классификации опухолей слюнных желез. В данной работе обобщены данные научной литературы о MASC-карциноме слюнных желез, в частности о ее гистологических, молекулярно-генетических особенностях, возможностях ее диагностики и лекарственной терапии. На клиническом примере продемонстрирована успешность применения энтректиниба (ингибитора тирозинкиназ при слияниях в генах NTRK1, NTRK2, NTRK3) у пациента со слиянием ETV6-NTRK3, выявленным при секвенировании нового поколения (next-generation sequencing). Секвенирование нового поколения позволяет определить молекулярно-генетические особенности редких опухолей, что открывает возможности для эффективной индивидуализированной терапии. Верификация MASC-карцином и определение их молекулярно-генетических характеристик имеет большое значение для прогноза, так как выявление характерного для данного подтипа слияния генов ETV6-NTRK3 и, соответственно, назначение таргетной терапии ингибиторами тирозинкиназ (энтректинибом, ларотректинибом) улучшает прогноз. В приведенном клиническом случае, несмотря на высокую клиническую эффективность таргетной терапии и быстрый ответ опухоли, наблюдалось постепенное развитие резистентности вследствие появления мутации G623R в гене NTRK3, которая снизила чувствительность опухоли к препарату. Таким образом, актуально дальнейшее изучение эффективности таргетной терапии, в том числе 2-го поколения, у пациентов с редкими опухолями и слияниями NTRK.

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