DNA修复抑制剂:针对性放射性核素治疗的潜在目标和合作伙伴
Honoka Obata1,2,3,4, Mikako Ogawa4, Michael R Zalutsky3
1Department of Advanced Nuclear Medicine Sciences, National Institutes for Quantum Science and Technology (QST), 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan.
Pharmaceutics
|July 29, 2023
概括
向癌细胞中的DNA维护因子可以提高向放射性核素治疗 (TRT) 的有效性. 抑制这些对癌症生存至关重要的因素,为克服治疗耐药性和提高TRT结果提供了一个有希望的策略.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 放射化学 放射化学是指辐射化学.
背景情况:
- 向放射性核素治疗 (TRT) 面临的局限性是由于癌细胞能够在高剂量辐射下生存.
- 瘤异质性和辐射/耐药细胞的发展降低了TRT的疗效.
- 癌细胞拥有强大的DNA损伤反应/修复机制,促进生存.
研究的目的:
- 确定潜在的分子点,以加强未来的向放射性核素治疗 (TRT) 策略.
- 探索DNA损伤反应/修复和维护系统在癌细胞存活中的作用.
- 通过将TRT与向抑制癌症生存因素相结合,提出新的治疗方法.
主要方法:
- 审查有关癌症基因组学,DNA损伤反应途径和TRT的当前文献.
- 对参与癌细胞存活和抗治疗的关键因素的分析.
- 确定TRT的潜在分子标和组合策略.
主要成果:
- 癌细胞固有的DNA修复机制和失调的表观遗传系统有助于TRT耐药性.
- 包括PARP,ATM/ATR,转录因子和DNA甲基转移酶在内的关键分子标与癌症生存有关.
- 抑制这些目标,特别是使用非放射性物质,显示了与TRT.有协同效应的潜力.
结论:
- 针对DNA维护因子是一个有前途的策略,可以克服TRT的局限性并改善患者的治疗结果.
- 将TRT与DNA修复和表观遗传机制的抑制剂结合起来可以提高治疗疗效.
- 未来的TRT策略应该考虑针对癌症特异性生存机制,以改善治疗反应.
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