International Journal of
Reproductive Biomedicine
Fri, Aug 7, 2026
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Volume 24, Issue 6 (June 2026)
IJRM 2026, 24(6): 0-0 |
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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-en.html
URL: http://ijrm.ir/article-1-3731-en.html
Mandana Zafari1 
, Hooman Zarei2 , Elham Sadeghi3 , Fatemeh Lotfi Asrami4 , Farima Bahmani5 , Saleheh Jahani6 , Dhifaf Saleem Kareem Maliki7 , Hadis Musavi *8 , Amirsaleh Abdollahi7
, Hooman Zarei2 , Elham Sadeghi3 , Fatemeh Lotfi Asrami4 , Farima Bahmani5 , Saleheh Jahani6 , Dhifaf Saleem Kareem Maliki7 , Hadis Musavi *8 , Amirsaleh Abdollahi7
1- Department of Midwifery, Sar.C., Islamic Azad University, Sari, Iran. & Health Reproductive Research Center, Sari Branch, Islamic Azad University, Sari, Iran.
2- Department of Anatomical Sciences, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran. & Immunogenetic Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
3- Department of Anatomical Sciences, School of Medicine, Ilam University of Medical Sciences, Ilam, Iran.
4- Department of Clinical Biochemistry, Faculty of Medicine, Golestan University of Medical Sciences, Golestan, Iran.
5- Department of Biochemistry, Faculty of Medicine, Semnan University of Medical Sciences, Semnan, Iran.
6- Visiting Scholar at the Pathology Department of the University of California, San Dieg, USA.
7- Department of Clinical Biochemistry and Genetics, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
8- Immunogenetic Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran. & Department of Clinical Biochemistry and Genetics, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran. ,msc.musavi66@gmail.com; h.mousavi@mazums.ac.ir
2- Department of Anatomical Sciences, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran. & Immunogenetic Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
3- Department of Anatomical Sciences, School of Medicine, Ilam University of Medical Sciences, Ilam, Iran.
4- Department of Clinical Biochemistry, Faculty of Medicine, Golestan University of Medical Sciences, Golestan, Iran.
5- Department of Biochemistry, Faculty of Medicine, Semnan University of Medical Sciences, Semnan, Iran.
6- Visiting Scholar at the Pathology Department of the University of California, San Dieg, USA.
7- Department of Clinical Biochemistry and Genetics, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
8- Immunogenetic Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran. & Department of Clinical Biochemistry and Genetics, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran. ,
Abstract: (18 Views)
The DNA damage response (DDR) is a fundamental cellular network that preserves genomic integrity, and its dysregulation drives initiation, progression, and therapeutic response in female reproductive system and breast cancers. This narrative review provides a comparative analysis of DDR alterations across ovarian, endometrial, cervical, and breast cancers, synthesizing molecular studies, clinical trials, and international guidelines from PubMed/MEDLINE, Scopus, and Web of Science. DDR alterations vary substantially among these cancers, reflecting differences in tissue origin, hormonal regulation, and viral oncogenesis. Homologous recombination repair defects, particularly in breast cancer susceptibility 1/2, partner and localizer of BRCA2, ataxia telangiectasia mutated, and checkpoint kinase 2), are prevalent in ovarian, endometrial, and breast cancers, predicting sensitivity to platinum-based chemotherapy and poly (ADP-ribose) polymerase inhibitors. In endometrial cancer, homologous recombination deficiency predominates in high-grade tumor protein p53-mutated subtypes, while Fanconi anemia pathway alterations characterize aggressive serous carcinomas. Cervical cancer exhibits virus-induced DDR disruption and replication stress. Quantitative biomarkers, including tumor mutational burden, microsatellite instability, Radiation sensitive 51, Fanconi anemia complementation group D2, excision repair cross-complementation group 1, and DDR-related microRNAs enable patient stratification. Emerging ataxia telangiectasia and Rad3-related and WEE1 inhibitors show promise in combination regimens. Understanding of tumor-specific DDR enables rational therapeutic stratification, providing a framework for precision oncology.
Keywords: DNA damage response, Ovarian neoplasms, Endometrial neoplasms, Cervical neoplasms, Breast neoplasms.
Type of Study: Review Article |
Subject:
Reproductive Oncology
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