在衰老和癌症中ATM和p53:基因组完整性的双刃剑
Surya Nath Pandey1, Muhammad Afzal2, Jyoti Uikey3
1Department of Pharmacology, Teerthanker Mahaveer College of Pharmacy, Teerthanker Mahaveer University, Moradabad, 244001, Uttar Pradesh, India.
Biogerontology
|May 5, 2025
概括
ATM-p53轴通过感知DNA损伤并启动修复或亡来维持基因组的稳定性. 失调有助于癌症,但针对ATM和p53提供治疗潜力.
科学领域:
- 基因组稳定性和DNA损伤反应.
- 癌症生物学和瘤进展.
- 细胞衰老和细胞亡.
背景情况:
- 基因组稳定性至关重要,涉及DNA损伤检测和响应途径,如ATM-p53.
- ATAM (突变的阿塔克西亚-太长叶病) 和p53是DNA修复,亡和衰老的关键调节者.
- ATM或p53中的突变会破坏这些过程,导致基因组不稳定性,癌症和治疗耐药性.
研究的目的:
- 审查ATM和p53在瘤抑制和癌症进展中的双重作用.
- 巩固ATM-p53协调在DNA修复,亡和衰老中的发现.
- 突出针对ATM-p53途径进行癌症治疗的治疗策略.
主要方法:
- 关于ATM和p53.53的最新发现的文献综述.
- 分析ATM-p53信号在DNA修复,亡和衰老中的作用.
- 检查针对ATM和p53.53的治疗方法.
主要成果:
- 亚马逊机械 (ATM) 无活化绕过瘤基因诱导的衰老,促进瘤的形成.
- p53突变驱动不受控制的增殖和对亡的抵抗.
- 持续的ATM信号可以诱导与衰老相关的分泌表型 (SASP),增强炎症和癌症进展.
- 小分子ATM抑制剂和p53激活剂使癌症对破坏DNA的疗法敏感.
- 在瘤扩散中ATM损失的确切作用可能取决于情境,可能在某些癌症中促进瘤抑制.
结论:
- ATM-p53轴在瘤抑制和癌症进展方面具有复杂的,取决于背景的作用.
- 了解ATM-p53协调对于开发有效的癌症疗法至关重要.
- 针对ATM和p53通路提供了有希望的策略,通过利用衰老和亡来提高癌症治疗结果.
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