جمعه 16 مرداد 1405
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دوره 24، شماره 6 - ( 3-1405 )
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Zafari M, Zarei H, Sadeghi E, Lotfi Asrami F, Bahmani F, Jahani S, et al . An overview of the DNA damage response in female reproductive system and breast cancers: A narrative review. IJRM 2026; 24 (6)
URL: http://ijrm.ir/article-1-3731-fa.html
URL: http://ijrm.ir/article-1-3731-fa.html
مروری بر پاسخ به آسیب DNA در سیستم تولیدمثل زنان و سرطانهای پستان: یک مرور روایی. International Journal of Reproductive BioMedicine. 1405; 24 (6)
چکیده: (17 مشاهده)
پاسخ به آسیب DNA (DDR) یک شبکه سلولی بنیادی است که از یکپارچگی ژنومی محافظت و اختلال در عملکرد آن، در شروع، پیشرفت و پاسخ درمانی سرطانهای سیستم تولیدمثل زنان و سرطان پستان نقش مهمی ایفا میکند. این مرور روایی، با هدف ارائه یک تحلیل مقایسهای از تغییرات مسیر DDR در سرطانهای تخمدان، آندومتر، دهانه رحم و پستان انجام شده و یافتههای مطالعات مولکولی، کارآزماییهای بالینی و دستورالعملهای بینالمللی استخراجشده از پایگاههای PubMed/MEDLINE،Scopus و Web of Science را تلفیق میکند. تغییرات مسیر DDR در میان این سرطانها بهطور قابلتوجهی متفاوت است که نشاندهنده تفاوت در منشأ بافتی، تنظیمات هورمونی و مکانیسمهای سرطانزایی ویروسی است. نقص در ترمیم نوترکیبی همولوگ بهویژه در ژنهای BRCA1/2، PALB2، ATM و CHEK2 در سرطانهای تخمدان، آندومتر و پستان شایع است و میتواند حساسیت به شیمیدرمانی مبتنی بر ترکیبات پلاتین و مهارکنندههای PARP را پیشبینی کند. در سرطان آندومتر، نقص ترمیم نوترکیبی همولوگ بیشتر در زیرگروههای پرخطر با جهش TP53 مشاهده میشود، در حالیکه تغییرات مسیر Fanconi anemia از ویژگیهای کارسینومهای سروزی تهاجمی محسوب میشوند. سرطان دهانه رحم نیز با اختلال در مسیر DDR ناشی از عفونتهای ویروسی و ایجاد استرس همانندسازی DNA همراه است. نشانگرهای زیستی کمی شامل بار جهش توموری، ناپایداری ریزماهوارهای،RAD51 ، FANCD2، ERCC1 و میکروRNAهای مرتبط با DDR، امکان طبقهبندی بیماران و انتخاب درمانهای هدفمند را فراهم میکنند. مهارکنندههای نوظهور مسیرهای ATR و WEE1 در رژیمهای درمانی ترکیبی، نتایج امیدوارکنندهای نشان دادهاند. درک تفاوتهای اختصاصی DDR در هر نوع تومور، امکان انتخاب منطقیتر درمانها را فراهم کرده و چارچوبی برای پزشکی دقیق در سرطانشناسی ارائه میدهد.
واژههای کلیدی: پاسخ به آسیب DNA، نئوپلاسمهای تخمدان، نئوپلاسمهای آندومتر، نئوپلاسمهای دهانه رحم، نئوپلاسمهای پستان.
نوع مطالعه: Review article |
فهرست منابع
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