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<p>Our study elucidates the role of FOXP1 in chemoresistance in small cell lung cancer(SCLC). FOXP1 enhances chemoresistance by regulating SP8 expression through its super-enhancer (SP8-SE), with SP8 mediating resistance via the homologous recombination repair (HRR) pathway. We also discovered that FOXP1 forms punctate nuclear structures indicative of liquid-liquid phase separation, crucial for its transcriptional regulation. Targeting the FOXP1-SP8-HR axis with BRD4 and PARP inhibitors showed synergistic effects in reducing tumor growth in vitro and in patient-derived xenograft models. These findings identify FOXP1 as a critical mediator and marker of chemoresistance in SCLC, providing a foundation for developing targeted therapies to overcome this resistance.</p>

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Targeting FOXP1 phase separation in small cell lung cancer mechanisms of chemotherapy resistance

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年3月13日

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  • Yichun Tang,
  • Yuchun Niu,
  • Yi Chen,
  • Xuyang Zhou,
  • Yueyang Hu,
  • Lei Sun,
  • Yan Xiong,
  • Yue Xu,
  • Qiongyao Wang,
  • Yu Wang,
  • Linlang Guo

摘要

Our study elucidates the role of FOXP1 in chemoresistance in small cell lung cancer(SCLC). FOXP1 enhances chemoresistance by regulating SP8 expression through its super-enhancer (SP8-SE), with SP8 mediating resistance via the homologous recombination repair (HRR) pathway. We also discovered that FOXP1 forms punctate nuclear structures indicative of liquid-liquid phase separation, crucial for its transcriptional regulation. Targeting the FOXP1-SP8-HR axis with BRD4 and PARP inhibitors showed synergistic effects in reducing tumor growth in vitro and in patient-derived xenograft models. These findings identify FOXP1 as a critical mediator and marker of chemoresistance in SCLC, providing a foundation for developing targeted therapies to overcome this resistance.