phgenomicsФармакогенетика и фармакогеномикаPharmacogenetics and Pharmacogenomics2588-05272686-8849LLC "Izdatelstvo OKI"phgenomics-34Research ArticleАКТУАЛЬНЫЕ ОБЗОРЫCURRENT REVIEWФармакогенетические особенности II фазы биотрансформации тамоксифена: систематический обзорPharmacogenetic features of the phase II biotransformation of tamoxifen: a systematic reviewСавельеваМарина ИвановнаSavelyevaM. I.marinasavelyeva@mail.ruУрванцеваИ. А.UrvantsevaI. A.noemail@neicon.ruИгнатоваА. К.IgnatovaA. K.noemail@neicon.ruПанченкоЮ. С.PanchenkoJ. S.noemail@neicon.ruПоддубнаяИ. В.PoddubnayaI. V.noemail@neicon.ruФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования» Минздрава РоссииРоссияThe Sechenov’ First State Medical UniversityRussian FederationФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М. Сеченова» Минздрава РоссииРоссияRussian Medical Academy of Postgraduate StudyRussian Federation201712032017011015Copyright © Савельева М.И., Урванцева И.А., Игнатова А.К., Панченко Ю.С., Поддубная И.В., 20172017Савельева М.И., Урванцева И.А., Игнатова А.К., Панченко Ю.С., Поддубная И.В.Savelyeva M.I., Urvantseva I.A., Ignatova A.K., Panchenko J.S., Poddubnaya I.V.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.pharmacogenetics-pharmacogenomics.ru/jour/article/view/34

Рак молочной железы - одна из ведущих причин смертности у женщин, поэтому эндокринное лечение имеет большую терапевтическую ценность у пациентов с эстроген-положительными опухолями. Тамоксифен, обладающий антиэстрогенной активностью, широко метаболизируется у пациентов с образованием активных соединений, имеющих изменённую афинность к рецепторам эстрогена. Кроме того, для его активных метаболитов характерен частичный эстрогенный эффект на эндометрий, что приводит к развитию гиперпластических процессов. Межличностная и межэтническая изменчивость фармакокинетики и фармакодинамики тамоксифена является причиной разнообразия терапевтического ответа, показателей смертности и выживаемости. Роль ферментов метаболизма тамоксифена I фазы активно изучается, но большинство исследователей сходятся во мнении, что ферменты I фазы и их метаболиты лишь частично объясняют механизмы патологического ответа пациентов на терапию тамоксифеном. Поэтому в данной статье основное внимание будет уделено сульфотрансферазам (SULT) и глюкуронилтрансферазам (UGT) -ферментам метаболизма тамоксифена II фазы, семейства которых будут определены, а также клиническому полиморфизму генов этих ферментов (SULT1A*2, SULT1A2*2, SULT1A2*3, UGT-48Val, UGT2B7-268Tyr, UGT2B15-523Thr).

Breast cancer remains one of the first leading causes of death in women, and currently endocrine treatment is of major therapeutic value in patients with estrogen-receptor positive tumors. The antiestrogen tamoxifen is extensively metabolized in patients to form a series of compounds with altered affinity for estrogen receptors (ERs), the primary target of this drug. Furthermore, these metabolites exhibit a range of partial agonist activity for ER in endometrium, which can lead to hyperplastic processes. Interindividual and interethnic variability of tamoxifen pharmacokinetics and pharmacodynamics is the cause of a variety of therapeutic response, mortality and survival rates. The role of enzymes for metabolism of tamoxifen I phase is actively being studied, but most researchers agree that the enzymes of the phase I and their metabolites only partially explain the mechanisms of the pathological response of patients to tamoxifen therapy. This article will focus on the sulfotransferases (SULT) and glucuronosyltransferases (UGT) - enzymes of the phase II metabolism of tamoxifen, whose family will be determined and also the clinically relevant polymorphism of the genes of these enzymes (SULT1A*2, SULT1A2*2, SULT1A2*3, UGT-48Val, UGT2B7-268Tyr, UGT2B15-523Thr).

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