DNA damage repair plays a key role in maintaining genomic stability and integrity. Flap endonuclease 1 (FEN1) is a core protein in the base excision repair (BER) pathway and participates in Okazaki fragment maturation during DNA replication. Several studies have implicated FEN1 in the regulation of other DNA repair pathways, including homologous recombination repair (HRR) and non-homologous end joining (NHEJ). Abnormal expression or mutation of FEN1 in cells can cause a series of pathological responses, leading to various diseases, including cancers. Moreover, overexpression of FEN1 contributes to drug resistance in several types of cancers. All this supports the hypothesis that FEN1 could be a therapeutic target for cancer treatment. Targeting FEN1 has been verified as an effective strategy in mono or combined treatment of cancer. Small-molecule compounds targeting FEN1 have also been developed and detected in cancer regression. In this review, we summarize the recent development of small-molecule inhibitors targeting FEN1 in recent years, thereby expanding their therapeutic potential and application.

中文翻译：

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靶向 FEN1 的小分子抑制剂用于癌症治疗

DNA 损伤修复在维持基因组稳定性和完整性方面起着关键作用。Flap 核酸内切酶 1 (FEN1) 是碱基切除修复 (BER) 途径中的核心蛋白，在 DNA 复制过程中参与 Okazaki 片段的成熟。几项研究表明 FEN1 参与了其他 DNA 修复途径的调节，包括同源重组修复 (HRR) 和非同源末端连接 (NHEJ)。FEN1在细胞中的异常表达或突变会引起一系列病理反应，导致各种疾病，包括癌症。此外，FEN1 的过表达有助于几种癌症的耐药性。所有这些都支持了 FEN1 可能成为癌症治疗的治疗靶点的假设。靶向 FEN1 已被证实是单一或联合治疗癌症的有效策略。靶向 FEN1 的小分子化合物也已开发并在癌症消退中检测到。在这篇综述中，我们总结了近年来针对 FEN1 的小分子抑制剂的最新发展，从而扩大了它们的治疗潜力和应用。