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Dr. Zhigang Guo’s team reveals that FEN1 inhibitor synergizes with low-dose camptothecin to induceincreased cell killing via the mitochondria mediated apoptotic pathway

Camptothecin has been used in tumor therapy for a long time but its antitumor effect is rather limited due to the side effect and the drug resistance. FEN1, a major component of DNA repair systems, plays important roles in maintaining genomic stability via DNA replication and repair. Here we found that FEN1 inhibitor greatly sensitizes cancer cells to low-dose camptothecin. The combinative treatment of FEN1 inhibitor and 1 nM camptothecin induced a synthetic lethal effect, which synergistically suppressed cancer cell proliferation and significantly mediated apoptosis both in vitro and in vivo. Our study suggested that targeting FEN1 could be a potent strategy for tumor-targeting cancer therapy. This paper has been recently published on line: https://doi.org/10.1038/s41434-020-00215-9