重温TGFβ悖论:从HPV驱动的癌症和DNA损伤反应的见解
Mary Helen Barcellos-Hoff1, Sue S Yom2
1Department of Radiation Oncology, University of California, San Francisco, San Francisco, CA, USA. maryhelen.barcellos-hoff@ucsf.edu.
Nature reviews. Cancer
|May 19, 2025
概括
矛盾的是,转化生长因子-β (TGFβ) 抑制健康组织,但促进已建立的癌症. 针对TGFβ的目标
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 癌症研究 癌症研究
背景情况:
- 转化生长因子-β (TGFβ) 悖论描述了它在癌症中的双重作用:在健康组织中抑制和在已建立的恶性瘤中促进.
- 由于缺乏患者选择标准,TGFβ抑制剂在临床试验中表现出有限的成功.
- 了解TGFβ在DNA修复中的作用对于开发向癌症疗法至关重要.
研究的目的:
- 探索向TGFβ调节人类乳头瘤病毒 (HPV) 驱动的头角状细胞癌 (HNSCC) 的治疗潜力.
- 审查TGFβ信号损失如何影响DNA修复及其对合成致死性诱导的潜力.
- 调查TGFβ在预测免疫检查点抑制剂反应中的作用以及生物标志物的实用性,用于患者选择.
主要方法:
- 对TGFβ信号传导,DNA修复机制和HPV驱动的HNSCC现有文献的审查.
- 分析HPV,TGFβ抑制和DNA损伤修复途径之间的相互作用.
- 探索针对DNA修复缺陷的合成致命性策略.
- 评估TGFβ对免疫检查点抑制剂反应的预测价值.
主要成果:
- HPV 抑制 TGFβ 信号传递,导致 HNSCC 中的 DNA 损伤修复减少.
- 这种DNA修复缺陷为癌症治疗提供了敏感性,并有助于HPV阳性HNSCC的良好预后.
- 针对TGFβ损失引起的DNA修复缺陷,提供了一个潜在的合成杀伤性策略.
- TGFβ通路状态可以预测对免疫检查点抑制剂的反应.
结论:
- TGFβ在癌症中的复杂作用需要精细的治疗策略.
- 针对由TGFβ途径改变引起的DNA修复缺陷,对于特定的癌症类型来说是一个有前途的方法.
- 生物标志物对于识别可能受益于TGFβ向治疗的患者至关重要,包括免疫检查点抑制剂.
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