To improve
breast cancer treatment and to enable new strategies for therapeutic resistance, therapeutic targets are constantly being studied. Potential targets are
proteins of DNA repair and replication and genomic integrity, such as
Flap Endonuclease 1 (FEN1). This study investigated the effects of FEN1 inhibitor FEN1-IN-4 in combination with ionizing radiation on cell death, clonogenic survival, the cell cycle, senescence, doubling time,
DNA double-strand breaks and micronuclei in
breast cancer cells, breast cells and healthy skin fibroblasts. Furthermore, the variation in the baseline FEN1 level and its influence on treatment prognosis was investigated. The cell lines show specific response patterns in the aspects studied and have heterogeneous baseline FEN1 levels. FEN1-IN-4 has cytotoxic,
cytostatic and
radiosensitizing effects, expressed through increasing cell death by apoptosis and
necrosis, G2M share, senescence, double-strand breaks and a reduced survival fraction. Nevertheless, some cells are less affected by the cytotoxicity and fibroblasts show a rather limited response. In vivo, high FEN1
mRNA expression worsens the prognosis of
breast cancer patients. Due to the increased expression in
breast cancer tissue, FEN1 could represent a new
tumor and prognosis marker and FEN1-IN-4 may serve as a new potent agent in
personalized medicine and targeted
breast cancer therapy.