Cellular senescence and cancer chemotherapy resistance.
Cellular senescence and cancer chemotherapy resistance.
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DOI：
10.1016/j.drup.2012.01.002
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发表时间：
2012-02
影响因子：
24.3
通讯作者：
Nelson, Peter S.
中科院分区：
文献类型：
--
作者：
Gordon, Ryan R.;Nelson, Peter S.
对癌症治疗剂的先天性或获得性抗性仍然是生物医学研究的重要领域，其对改善癌症特异性死亡率具有明确的影响。重要的是，关键抗性机制的线索可能在于对损伤和应激的精心策划和高度保守的细胞和系统反应。许多抗肿瘤疗法通常依赖于DNA损伤，其涉及有效的DNA损伤应答信号传导途径，其在检查点处最终导致细胞凋亡或生长停滞以允许损伤修复。然而，当受到这些内部/外部压力的挑战时，也可以启动另一种细胞反应衰老，并且在理想情况下作为自我保护机制。衰老诱导疗法是一个有吸引力的概念，因为它们代表了对压倒性遗传毒性应激或癌基因激活的正常、高度保守和常见的肿瘤抑制反应。然而，这些方法应确保不会发生衰老旁路或衰老再出现，因为出现的细胞似乎具有高度耐药表型。此外，在某些情况下，细胞非自主衰老反应可能导致治疗抗性。在这里，我们提供了一个概述的机制，细胞衰老可能有助于治疗阻力和概念，衰老反应可以影响改善癌症治疗结果。
Innate or acquired resistance to cancer therapeutics remains an important area of biomedical investigation that has clear ramifications for improving cancer specific death rates. Importantly, clues to key resistance mechanisms may lie in the well-orchestrated and highly conserved cellular and systemic responses to injury and stress. Many anti-neoplastic therapies typically rely on DNA damage, which engages potent DNA damage response signaling pathways that culminate in apoptosis or growth arrest at checkpoints to allow for damage repair. However, an alternative cellular response, senescence, can also be initiated when challenged with these internal/external pressures and in ideal situations acts as a self-protecting mechanism. Senescence-induction therapies are an attractive concept in that they represent a normal, highly conserved and commonly-invoked tumor-suppressing response to overwhelming genotoxic stress or oncogene activation. Yet, such approaches should ensure that senescence by-pass or senescence re-emergence does not occur, as emergent cells appear to have highly drug resistant phenotypes. Further, cell non-autonomous senescence responses may contribute to therapy-resistance in certain circumstances. Here we provide an overview of mechanisms by which cellular senescence plausibly contributes to therapy resistance and concepts by which senescence responses can be influenced to improve cancer treatment outcomes.
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影响因子：
78.5
作者：
Collado, Manuel;Serrano, Manuel
通讯作者：
Serrano, Manuel
影响因子：
11.2
作者：
Bavik, C;Coleman, I;Nelson, PS
通讯作者：
Nelson, PS
影响因子：
64.8
作者：
Bartkova, Jirina;Rezaei, Nousin;Gorgoulis, Vassilis G.
通讯作者：
Gorgoulis, Vassilis G.
影响因子：
10.5
作者：
Chien, Yuchen;Scuoppo, Claudio;Lowe, Scott W.
通讯作者：
Lowe, Scott W.
影响因子：
78.5
作者：
Chabner, BA;Roberts, TG
通讯作者：
Roberts, TG