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

SYCP3是联会复合体的组成部分之一，联会复合体是减数分裂重组所必需的结构。该蛋白在正常有丝分裂细胞中不表达，但在各种癌症中异常表达。由于我们已经发现SYCP3通过干扰BRCA2抑制有丝分裂细胞中的同源重组，在本研究中，我们检测了表达SYCP3的有丝分裂细胞对PARP抑制剂或PARP抑制剂和通过诱导DNA双链断裂而发挥抗肿瘤活性的药物的联合治疗是否敏感。表达SYCP3的细胞对PARP抑制剂NU1025表现出极高的超敏反应，辐射或顺铂预处理可显著增强这种超敏反应。这些发现将为开发SYCP3表达肿瘤的新疗法提供分子基础。

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.