Ukr.Biochem.J. 2020; Том 92, № 6, листопад-грудень, c. 53-62

doi: https://doi.org/10.15407/ubj92.06.053

Реплікативна CMG-геліказа: ідеальна мішень для таргетної терапії раку

23.02.2021   Uncategorized   No comments

W. Henderson, K. Nyman, M. Stoney, S. I. Borysov*

College of Arts and Sciences, Saint Leo University, St. Leo, Florida, USA;
*e-mail: Sergiy.Borysov@saintleo.edu

Отримано: 31 травня 2020; Затверджено: 13 листопада 2020

Огляд присвячено Cdc45-Mcm2-7-GINS (CMG) геліказі, яка є важливою складовою  реплікативного механізму і розглядається як нова перспективна мішень для таргетної терапії раку. У нормальних клітинах під час реплікації геному поступово, шляхом залучення необхідної кількості субодиниць,  активується лише невелика частина геліказ, решта складають значний пул сплячих геліказ та можуть бути активовані у разі необхідності  для  заміщення геліказ із пригніченою активністю, завдяки чому нормальна клітина має стійкість до інгібіторів геліказ. Відомо, що на відміну від нормальних клітин  ракові клітини мають значно менший пул сплячих геліказ і через це мають бути вразливішими до інгібіторів CMG-геліказ. Функціональні дослідження підтверджують, що таргетне пригнічення CMG-гелікази може стати специфічним терапевтичним підходом у подоланні  широкого спектра онкологічних захворювань та у мінімізації побічних ефектів. Передбачається, що препарати спрямованої дії на CMG-геліказу можуть використовуватися не тільки для самостійної терапії, а й як хіміосенсибілізатори в поєднанні з іншими ліками для підвищення їх клінічного ефекту.

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