Senolytics for Cancer Therapy: Is All That Glitters Really Gold?
Senolytics for Cancer Therapy: Is All That Glitters Really Gold?
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DOI：
10.3390/cancers13040723
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发表时间：
2021-02-10
期刊：
影响因子：
5.2
通讯作者：
Gewirtz DA
中科院分区：
文献类型：
--
作者：
Carpenter VJ;Saleh T;Gewirtz DA
衰老是肿瘤细胞生物学的重要组成部分，是对治疗的主要细胞应激反应。虽然衰老在癌症治疗中的长期影响尚未完全了解，但选择性杀死衰老细胞的药物senolytics的使用是癌症治疗中的一个积极研究领域。目前的临床前文献中出现了一些挑战和未回答的问题，表明需要重新评估一些基本前提和实验方法，以及将senolytics作为当前癌症治疗的佐剂应用于临床的潜在效用。Senolytics代表了一组机制不同的药物，可以消除衰老细胞，无论是在肿瘤和几个衰老相关的病理。因此，已提出使用senolytic作为一种潜在的辅助方法，以改善对衰老诱导的常规和靶向癌症治疗的反应。尽管senolytics的明确承诺，普遍性，选择性，耐药性和毒性的问题仍有待进一步澄清。在这篇综述中，我们试图总结和分析目前的临床前文献涉及使用senolytics衰老肿瘤细胞模型，并提出合理的解决方案和未来的方向，以提高理解和使用这类新的药物。
Senescence is an essential component of tumor cell biology and is a primary cell stress response to therapy. While the long-term impact of senescence in cancer therapy is not yet fully understood, the use of senolytics, drugs that selectively kill senescent cells, is an area of active investigation in cancer treatment. Several challenges and unanswered questions have arisen from the current preclinical literature, indicating the need to re-evaluate some of the basic premises and experimental approaches, as well as the potential utility for translating to the clinic the application of senolytics as adjuvants to current cancer therapy. Senolytics represent a group of mechanistically diverse drugs that can eliminate senescent cells, both in tumors and in several aging-related pathologies. Consequently, senolytic use has been proposed as a potential adjuvant approach to improve the response to senescence-inducing conventional and targeted cancer therapies. Despite the unequivocal promise of senolytics, issues of universality, selectivity, resistance, and toxicity remain to be further clarified. In this review, we attempt to summarize and analyze the current preclinical literature involving the use of senolytics in senescent tumor cell models, and to propose tenable solutions and future directions to improve the understanding and use of this novel class of drugs.
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影响因子：
64.8
作者：
Baker DJ;Childs BG;Durik M;Wijers ME;Sieben CJ;Zhong J;Saltness RA;Jeganathan KB;Verzosa GC;Pezeshki A;Khazaie K;Miller JD;van Deursen JM
通讯作者：
van Deursen JM
影响因子：
3.4
作者：
Alotaibi M;Sharma K;Saleh T;Povirk LF;Hendrickson EA;Gewirtz DA
通讯作者：
Gewirtz DA
DOI：
10.1146/annurev-pathol-121808-102144
发表时间：
2010
期刊：
Annual review of pathology
影响因子：
--
作者：
Coppé JP;Desprez PY;Krtolica A;Campisi J
通讯作者：
Campisi J
影响因子：
11.4
作者：
Barascu, Aurelia;Le Chalony, Catherine;Bertrand, Pascale
通讯作者：
Bertrand, Pascale
影响因子：
6.2
作者：
Chandra, Abhishek;Lagnado, Anthony B.;Pignolo, Robert J.
通讯作者：
Pignolo, Robert J.