Fen1, also known as Flap endonuclease 1, is a core protein in the base excision repair (BER) pathway and is involved in Okazaki fragment maturation during DNA replication. It belongs to the Rad2 structure-specific nuclease family and has 5' flap endonuclease, 5'-3' exonuclease, and gap-endonuclease activities, allowing it to participate in multiple DNA metabolic pathways such as stalled replication fork rescue, telomere maintenance, and apoptotic DNA fragmentation [2,5]. It is crucial for maintaining genomic stability and integrity [3].

BRCA2-deficient cells selectively depend on Fen1, specifically requiring its 5' flap endonuclease activity but not the 5'-3' exonuclease activity. Chemically inhibiting Fen1 can selectively target BRCA-deficient cells, indicating its potential as a therapeutic target in cancers related to BRCA deficiency [1]. In hepatocellular carcinoma, upregulation of Fen1 mediated by SUMO2 promotes the stemness of hepatocellular carcinoma stem cells, and attenuation of Fen1 might offer a new approach for eliminating these cells [3]. In cholangiocarcinoma, FEN1 is highly expressed, promoting cell proliferation, migration, invasion, DNA damage repair, and aerobic glycolysis, and mediating epithelial-mesenchymal transition through the Wnt/β-catenin signaling pathway [4].

In conclusion, Fen1 plays essential roles in DNA repair and replication processes, which are crucial for maintaining genomic stability. Its significance in various cancer-related biological processes, such as in BRCA-deficient cancers, hepatocellular carcinoma, and cholangiocarcinoma, has been revealed through functional studies. Understanding Fen1's functions can provide new perspectives for cancer treatment strategies.