Development of a novel therapeutic strategy utilizing PARP inhibitors in combination with radiotherapy based on cancer-specific abnormalities in homologous recombination

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SYCP3 is one of the components of the synaptonemal complex, the structure essential for meiotic recombination. The protein is not expressed in normal mitotic cells, but is aberrantly expressed in various cancers. Since we have found that SYCP3 inhibits homologous recombination by interfering with BRCA2 in mitotic cells, in this study, we examined whether the mitotic cells expressing SYCP3 is sensitive to the PARP inhibitor or combination therapies of the PARP inhibitor and agents that exert anti-tumor activities by inducing DNA double-strand breaks. Cells expressing SYCP3 showed extreme hypersensitivity to the PARP inhibitor NU1025, and pretreatment with radiation or cisplatin markedly enhanced this hypersensitivity. These findings would serve as a molecular basis for developing novel therapies for SYCP3-expressing tumors.