Advances in Molecular OncologyAdvances in Molecular OncologyУспехи молекулярной онкологии2313-805X2413-3787Publishing House ABV Press6910.17650/2313-805X-2016-3-3-44-55REVIEW ARTICLESОБЗОРНЫЕ СТАТЬИSecond primary malignancies of cancer patients: treatment-related carcinogenesisВторые первичные опухоли у онкологических больных: лекарственный канцерогенез в онкологииBelitskiyG. A.БелицкийГ. А.
Russian Federation
belitsga@gmail.comLesovayaE. A.ЛесоваяЕ. А.
Russian Federation
KirsanovK. I.КирсановК. И.
Russian Federation
YakubovskayaM. G.ЯкубовскаяМ. Г.
Russian Federation
Research Institute of Carcinogenesis, N.N. Blokhin Russian Cancer Reseach Center, Ministry of Health of RussiaНаучно-исследовательский институт канцерогенеза ФГБУ «Российский онкологический научный центр им. Н. Н. Блохина» Минздрава России24 Kashirskoe Shosse, Moscow, 115478, RussiaРоссия, 115478, Москва, Каширское шоссе, 2424 Kashirskoe Shosse, Moscow, 115478, Russia I.P. Pavlov Ryazan’ State Medical University, Ministry of Health of RussiaРоссия, 115478, Москва, Каширское шоссе, 24 ФГБОУ ВО «Рязанский государственный медицинский университет им. акад. И.П. Павлова» Минздрава России9 Vasokovol’tnaya St., Ryazan’, 390026, RussiaРоссия, 390026, Рязань, ул. Высоковольтная, 9150920163344553009201630092016Copyright ©; 2016, Belitskiy G.A., Lesovaya E.A., Kirsanov K.I., Yakubovskaya M.G.Copyright ©; 2016, Белицкий Г.А., Лесовая Е.А., Кирсанов К.И., Якубовская М.Г.2016Belitskiy G.A., Lesovaya E.A., Kirsanov K.I., Yakubovskaya M.G.Белицкий Г.А., Лесовая Е.А., Кирсанов К.И., Якубовская М.Г.https://creativecommons.org/licenses/by/4.0https://umo.abvpress.ru/jour/article/view/69

Cytostatic drugs used in chemotherapy cause secondary tumors in some patients cured of the antecedent neoplasm. Thus the incidence of second neoplasia for cancer survivors compared with the general population represents a 4-fold to 6-fold increased risk.The review presents recent data on the mechanisms of malignant transformation of cells by cytostatics, on the characteristics of high- risk groups associated with congenital polymorphisms of xenobiotic metabolizing enzymes and DNA repair systems. Increased risk of drug-related cancer was observed in patients with high activity of P450 isoforms, transforming cytotoxic prodrugs into the active electrophilic metabolites and low level of detoxifying enzymes. All things being equal the risk of therapy related neoplasia is higher in patients with low activity of DNA repair enzymes. It is evaluated the possibility of experimental study of new targeted drugs carcinogenic potential in order to minimize the future risk of secondary malignancies.

Цитостатики, используемые в химиотерапии, вызывают образование вторых первичных опухолей у некоторых больных, излеченных от первого новообразования. При этом риск возникновения вторых опухолей после излечения от первых повышается в 4–6 раз по сравнению с общей популяцией. В обзоре приведены современные данные о механизме злокачественной трансформации клеток цитостатиками, группах повышенного риска, связанного с врожденным полиморфизмом систем метаболизма ксенобиотиков и репарацией повреждений ДНК. Наибольший риск лекарственных опухолей отмечен у пациентов с высокой активностью изоформ цитохрома Р450, превращающего транспортные формы цитостатиков в активные электрофильные метаболиты, и с низким уровнем детоксицирующих ферментов. При прочих равных условиях в группу повышенного риска входят больные с низкой активностью ферментов репарации ДНК. Рассматриваются возможности исследования канцерогенного потенциала новых таргетных препаратов в эксперименте в целях минимизации риска возникновения вторых опухолей, обусловленных лечением.

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