Cancer UrologyCancer UrologyОнкоурология1726-97761996-1812Publishing House ABV Press48110.17650/1726-9776-2015-11-4-34-41DIAGNOSIS AND TREATMENT OF URINARY SYSTEM TUMORS. RENAL CANCERДИАГНОСТИКА И ЛЕЧЕНИЕ ОПУХОЛЕЙ МОЧЕПОЛОВОЙ СИСТЕМЫ. Рак почкиPrognostic factors of the therapeutic efficacy of mTOR and VEGFR inhibitors in patients with metastatic renal cell carcinomaФакторы прогноза эффективности терапии ингибиторами mTOR и VEGFR у больных метастатическим почечно-клеточным ракомVoroshilovaЕ. А.ВорошиловаЕ. А.
Russian Federation
voroshilova_ea@mail.ruApanovichN. V.АпановичН. В.
Russian Federation
NosovD. A.НосовД. А.
Russian Federation
KarpukhinА. V.КарпухинА. В.
Russian Federation
SokolovaI. N.СоколоваИ. Н.
Russian Federation
FedyaninM. Yu.ФедянинМ. Ю.
Russian Federation
N.N. Blokhin Russian Cancer Research Center of the Ministry of Health of RussiaФГБУ «Российский онкологический научный центр им. Н.Н. Блохина» Минздрава России23 Kashirskoe Shosse, Moscow, 115478, RussiaРоссия, 115478, Москва, Каширское шоссе, 233012201511434411409201520102015https://oncourology.abvpress.ru/oncur/article/view/481

Background. Thorough study of the molecular genetic alterations in patients with hereditary and sporadic renal cell carcinoma (RCC) enabled to reveal potential therapeutic targets - vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), growth factor receptors (VEGFR, PDGFR, EGFR, FGFR), mTOR signaling protein. Advances in targeted therapy treatment in the current therapeutic practice have brought a problem of its rational use and ultimately effective outcomes. The main solution of solving this problem is to establish independent clinical and laboratory prognostic factors and molecular markers which could predict the efficacy of targeted therapy.

Objective – optimization of targeted therapy in patients with RCC by using both molecular and genetic prognostic factors as predictors of the treatment efficacy.

Materials and methods. We assessed the level of mRNA expression of 13 potential target genes in primary tumor and metastatic site of patients suffering from metastatic RCC (n = 43) and evaluated the influence of the selected genes’ expression on the therapeutic efficacy of mTOR inhibitors and VEGFR inhibitors.

Conclusion. VEGFR1 mRNA overexpression in metastatic site as well as mTOR and/or PI3K mRNA overexpression could be assessed as potential biomarkers in predicting the treatment efficacy of VEGFR inhibitors and mTOR inhibitors respectively. The higher expression of RAF1 mRNA and mTOR signaling pathway are not typical molecular alterations in patients with mRCC. RAF1 mRNA overexpression in metastatic site as well as activation of the alternative signaling pathway (RAS-RAF-MAPK) in tumor cell are negative prognostic factors of the efficacy of targeted therapy. Activation of the signaling RAS-RAF-MAPK pathway in tumor cells is probably an alternative independent mechanism that “drives” tumor development in certain groups of patients.

Введение. В результате изучения молекулярно-генетических нарушений у больных спорадическими и наследственными формами почечно-клеточного рака (ПКР) были выделены потенциальные мишени для противоопухолевого воздействия – фактор роста эндотелия сосудов (VEGF), тромбоцитарный фактор роста (PDGF), рецепторы к ростовым факторам (VEGFR, PDGFR, EGFR, FGFR), сигнальный белок mTOR. С появлением в клинической практике новых лекарственных препаратов возникла проблема их рационального использования с целью повышения эффективности терапии. Выделение независимых клинико-лабораторных факторов прогноза в сочетании с молекулярными маркерами, способными предсказать эффективность таргетных лекарственных подходов, являются основным инструментом для решения данной проблемы. Цель исследования – оптимизация таргетной терапии больных ПКР за счет использования молекулярно-генетических факторов прогнозирования эффективности лекарственного лечения.

Материалы и методы. Больным метастатическим ПКР (n = 43) выполнен анализ уровня экспрессии мРНК 13 потенциальных генов-мишеней в ткани первичной опухоли и в ткани метастаза и оценено влияние уровня экспрессии мРНК данных генов на эффективность терапии ингибитором mTOR и ингибиторами VEGFR.

Заключение. Гиперэкспрессия мРНК VEGFR1 в ткани метастаза и гиперэкспрессия мРНК mTOR и/или PI3K могут рассматриваться в качестве потенциальных биомаркеров, прогнозирующих эффективность терапии ингибиторами VEGFR и ингибиторами mTOR соответственно. Гиперэкспрессия мРНК RAF1 и гиперэкспрессия мРНК генов mTOR-зависимого сигнального пути – взаимоисключающие молекулярные нарушения у больных метастатическим ПКР. Гиперэкспрессия мРНК RAF1 в ткани метастаза и соответственно активация альтернативного сигнального пути (RAS-RAF-MAPK) в опухолевой клетке являются факторами, которые имеют отрицательное прогностическое значение при проведении таргетной терапии. Вероятно, активация сигнального пути RAS-RAF-MAPK в опухолевых клетках служит альтернативным самостоятельным «драйверным» механизмом развития опухоли у отдельных больных.

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