Borderline ovarian tumors are a special class of ovarian tumors between benign and malignant, which are not sensitive to traditional chemotherapy regimens, and the development of target drugs is limited due to the lack of cell lines. Tumor organoids can well preserve the genetic characteristics of the primary tumor, but there are only a few reports of application in borderline tumors. In this study, we successfully generated 13 ovarian borderline tumor organoids and tested the antitumor activity of Bractoppin, a BRCA1 carboxy-terminal domain (BRCT) inhibitor. Bractoppin promotes organoid apoptosis. Mechanistically, Bractoppin can inhibit organoid cell cycle progression, inhibit the repair of DSB damage and promote tumor cell apoptosis. In addition, Bractoppin can also promote the apoptosis of ovarian cancer cell lines and inhibit the HR and NHEJ repair ability of tumor cells. We demonstrate the value of ovarian borderline tumor organoids in the exploration of molecular therapy drugs, and Bractoppin may be a valuable small molecule drug in the treatment of BOT.

卵巢交界性肿瘤是介于良性和恶性之间的一类特殊卵巢肿瘤，对传统化疗方案不敏感，且由于缺乏细胞系，靶向药物的开发受到限制。肿瘤类器官可以很好地保留原发肿瘤的遗传特征，但在交界性肿瘤中的应用报道较少。在这项研究中，我们成功地生成了 13 个卵巢交界性肿瘤类器官，并测试了 BRCA1 羧基末端结构域 (BRCT) 抑制剂 Bractoppin 的抗肿瘤活性。Bractoppin 促进类器官凋亡。从机制上讲，Bractoppin 可以抑制类器官细胞周期进程，抑制 DSB 损伤的修复，促进肿瘤细胞凋亡。此外，Bractoppin 还可以促进卵巢癌细胞系的凋亡，抑制肿瘤细胞的 HR 和 NHEJ 修复能力。我们证明了卵巢交界性肿瘤类器官在分子治疗药物探索中的价值，Bractoppin 可能是治疗 BOT 的有价值的小分子药物。