An overview of the DNA damage response in female reproductive system and breast cancers: A narrative review

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 ۱/۲, partner and localizer of BRCA۲, ataxia telangiectasia mutated, and checkpoint kinase ۲), 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 p۵۳-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 ۵۱, Fanconi anemia complementation group D۲, excision repair cross-complementation group ۱, and DDR-related microRNAs enable patient stratification. Emerging ataxia telangiectasia and Rad۳-related and WEE۱ inhibitors show promise in combination regimens. Understanding of tumor-specific DDR enables rational therapeutic stratification, providing a framework for precision oncology.

کلیدواژه ها:

DNA damage response ، Ovarian neoplasms ، Endometrial neoplasms ، Cervical neoplasms ، Breast neoplasms. ، پاسخ به آسیب DNA ، نئوپلاسم های تخمدان ، نئوپلاسم های آندومتر ، نئوپلاسم های دهانه رحم ، نئوپلاسم های پستان.