Potential role of Fanconi anemia pathway in the pathogenesis of endometrial cancer (Review).

Abstract

Endometrial cancer (EC) is a common gynecologic malignancy that often exhibits molecular features such as extensive somatic copy number alterations, microsatellite instability and frequent TP53 mutations, which considerably affect the physical and mental well‑being of women. The Fanconi anemia (FA) pathway is a DNA damage repair pathway involving multiple FA genes that play crucial roles in DNA damage repair as well as the maintenance of genome stability. Abnormalities in FA, such as deletions or mutations, may lead to defects in DNA damage repair, resulting in increased genomic instability and/or an abnormal cell cycle, ultimately leading to EC. This comprehensive review provides a systematic summary of EC‑related FA genes, elucidates the roles of various FA genes in EC and further speculates on their related mechanisms to facilitate the development of targeted therapies that specifically target key genes, leading to a more accurate and efficient treatment for EC. The present review searched PubMed and Google Scholar for articles published in English up to June 2025 using keywords such as Fanconi anemia pathway, 22 FA genes (FANCA, FANCB, FANCC, FANCD1/BRCA2, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCJ/BRIP1, FANCL, FANCM, FANCN/PALB2, FANCO/RAD51C, FANCP/SLX4, FANCQ/XPF, FANCR/RAD51, FANCS/BRCA1, FANCT/UBE2T, FANCU/XRCC2, FANCV/REV7, FANCW/RFWD3), endometrial cancer (type I: Endometrioid adenocarcinoma; Type II Uterine serous carcinoma, clear‑cell carcinoma, carcinosarcoma), somatic copy number alterations, microsatellite instability, TP53 mutations, pathogenesis, genomic instability, target therapy.