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<p>Drug resistance jeopardizes the prognosis of high-grade serous ovarian carcinoma (HGSOC) patients via DNA damage repair-coupled mechanism. The role of biomolecular phase separation in DNA damage repair has loomed. Here we find that CBX2 condensates are associated with drug resistance and contribute to DNA double-strand break (DSB) repair in HGSOC. Specifically, CBX2 condensates facilitate the recruitment of key DSB repair factors PARP1, 53BP1, and BRCA1 to chromatin. Patients with a CBX2-negative pattern exhibit the best prognosis, followed by those with non-condensate CBX2, while the worst outcomes are observed in patients with condensate CBX2. By drug screening, Ibrutinib is identified as an effective inhibitor of HGSOC cells and patient-derived organoids with CBX2 condensates. Overall, CBX2 phase separation enhances DSB repair-mediated drug resistance in HGSOC cells, and Ibrutinib may offer a viable therapeutic option for CBX2-positive HGSOC patients.</p>

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CBX2 phase-separation contributes to homologous recombination repair and drug resistance in ovarian cancer

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年3月26日

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  • Si Sun,
  • Lin Huang,
  • Yujia Ma,
  • Zheng Wei,
  • Mengna Zhu,
  • Mengqing Chen,
  • Feiquan Ying,
  • Xiaoling Zhou,
  • Ping Yang,
  • Yiping Wen,
  • Qiang Yang,
  • Liqiong Cai,
  • Yuan Zhang,
  • Jing Cai

摘要

Drug resistance jeopardizes the prognosis of high-grade serous ovarian carcinoma (HGSOC) patients via DNA damage repair-coupled mechanism. The role of biomolecular phase separation in DNA damage repair has loomed. Here we find that CBX2 condensates are associated with drug resistance and contribute to DNA double-strand break (DSB) repair in HGSOC. Specifically, CBX2 condensates facilitate the recruitment of key DSB repair factors PARP1, 53BP1, and BRCA1 to chromatin. Patients with a CBX2-negative pattern exhibit the best prognosis, followed by those with non-condensate CBX2, while the worst outcomes are observed in patients with condensate CBX2. By drug screening, Ibrutinib is identified as an effective inhibitor of HGSOC cells and patient-derived organoids with CBX2 condensates. Overall, CBX2 phase separation enhances DSB repair-mediated drug resistance in HGSOC cells, and Ibrutinib may offer a viable therapeutic option for CBX2-positive HGSOC patients.