Cancer UrologyCancer UrologyОнкоурология1726-97761996-1812Publishing House ABV Press32810.17650/1726-9776-2010-6-4-23-31DIAGNOSIS AND TREATMENT OF URINARY SYSTEM TUMORS. RENAL CANCERДИАГНОСТИКА И ЛЕЧЕНИЕ ОПУХОЛЕЙ МОЧЕПОЛОВОЙ СИСТЕМЫ. Рак почкиMOLECULAR BIOLOGICAL FACTORS OF PROGNOSIS AND EFFICIENCY OF MEDICAL TREATMENT FOR DISSEMINATED RENAL CELL CARCINOMAМОЛЕКУЛЯРНО-БИОЛОГИЧЕСКИЕ ФАКТОРЫ ПРОГНОЗА И ЭФФЕКТИВНОСТИ ЛЕКАРСТВЕННОГО ЛЕЧЕНИЯ ПРИ ДИССЕМИНИРОВАННОМ РАКЕ ПОЧКИNosovD. A.НосовД. А.
Russian Federation
nosov@mail.ruYakovlevaE. S.ЯковлеваЕ. С.
Russian Federation
nosov@mail.ruAtayevaD. A.АтаеваД. А.
Russian Federation
nosov@mail.ruLyubchenkoL. N.ЛюбченкоЛ. Н.
Russian Federation
nosov@mail.ruTyulyandinS. A.ТюляндинС. А.
Russian Federation
nosov@mail.ruDepartment of Clinical Pharmacology and ChemotherapyОтделение клинической фармакологии и химиотерапииLaboratory of Clinical Oncogenetics, N.N. Blokhin Russian Cancer Research Center, Russian Academy of Medical Sciences, MoscowЛаборатория клинической онкогенетики ГУ РОНЦ им. Н.Н. Блохина РАМН, Москва301220106423310608201406082014https://oncourology.abvpress.ru/oncur/article/view/328

The substantial improvement of treatment results in patients with disseminated forms of renal cell carcinoma (RCC) is associated with the active clinical application of target drugs that affect the molecular genetic mechanisms underlying the development of this disease. Inactivation of the VHL gene and/or the disorders related to other elements of the signaling pathway regulating the processes of proliferation and neoangionesis in tumor tissue (mammalian target of rapamycin; hypoxia-induced factor; vascular endothelial growth factor and its receptor; platelet-derived growth factor receptor; and carboanhydrase IX) are considered to be one of the early and key events in carcinogenesis in clear cell RCC. However, there is presently no consensus of opinion as the prognostic value of these disorders and their impact on the efficiency of drug therapy. The results of the clinical trials assessing potential molecular biological markers are discordant. This is attributable both to the dissimilar clinical characteristics of patients and different methodological approaches to evaluating these or those molecular impairments. There are also other alternative signaling pathways and mechanisms responsible for the formation of primary or secondary drug resistance when target agents are administered. Thus, the quest of potential biomarkers remains an urgent problem as before. This paper analyzes the results of the currently available clinical studies of the role of various biological markers in predicting the efficiency of the present-day medicinal approaches to treating patients with RCC.

Существенное улучшение результатов лечения пациентов с диссеминированными формами почечно-клеточного рака (ПКР) связано с активным использованием в клинической практике таргетных препаратов, оказывающих действие на молекулярно-генетические механизмы, которые лежат в основе развития данного заболевания. Одним из ранних и ключевых событий в канцерогенезе при светлоклеточном варианте ПКР считается инактивация VHL-гена и/или наличие нарушений, которые связаны с другими элементами сигнального пути, регулирующего процессы пролиферации и неоангиогенеза в опухолевой ткани (mTOR - mammalian target of rapamycin - мишень рапамицина в клетках млекопитающих, HIF - hypoxia-induced factor - индуцируемый гипоксией фактор, VEGF/VEGFR - vascular endothelial growth factor - сосудисто-эндотелиальный фактор роста и его рецептор, PDGFR - platelet-derived growth factor receptor - рецептор тромбоцитарного фактора роста, CA IX - карбоангидраза IX). Однако в настоящее время нет единого мнения о прогностической значимости данных нарушений и их влиянии на эффективность лекарственного лечения. Результаты проведенных клинических исследований, в которых оценивали потенциальные молекулярно-биологические маркеры, выглядят противоречивыми. Это может объясняться как разнородными клиническими характеристиками больных, так и различными методологическими подходами в оценке тех или иных молекулярных нарушений. Также существуют другие альтернативные сигнальные пути и механизмы, ответственные за формирование первичной или вторичной лекарственной резистентности при использовании таргетных агентов. Таким образом, проблема поиска потенциальных биомаркеров остается по-прежнему актуальной. В данной статье приводится анализ результатов доступных на сегодняшний день клинических исследований, в которых изучалась роль различных биологических маркеров в прогнозировании эффективности современных лекарственных подходов в лечении у больных ПКР.

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