Targeting the Mitotic Catastrophe Signaling Pathway in Cancer.
Targeting the Mitotic Catastrophe Signaling Pathway in Cancer.
复制标题
DOI：
10.1155/2015/146282
复制
发表时间：
2015
影响因子：
4.6
通讯作者：
Mc Gee MM
中科院分区：
文献类型：
--
作者：
Mc Gee MM
根据国际细胞死亡命名委员会 2012 年的定义，有丝分裂灾难是一种真正的内在肿瘤抑制机制，它能够感知有丝分裂失败，并通过驱动细胞走向不可逆转的死亡或衰老的抗增殖命运来做出反应。因此，有丝分裂失败的灾难可以促进缺陷细胞的无限制生长，从而成为肿瘤发展的主要途径。此外，有丝分裂灾难的激活提供了显着的治疗优势，该优势已在常规和靶向抗癌剂的作用中得到利用。然而，尽管有丝分裂灾难在肿瘤预防和治疗中很重要，但其分子机制尚不清楚。更好地理解有丝分裂失败或有缺陷后决定细胞命运的信号将揭示选择性靶向和增强治疗益处的计划的新机会，并揭示预测患者反应的生物标志物。这篇综述的重点是有丝分裂灾难诱导和信号转导的分子机制，并强调了当前在癌症治疗中利用这一过程的策略。
Mitotic catastrophe, as defined in 2012 by the International Nomenclature Committee on Cell Death, is a bona fide intrinsic oncosuppressive mechanism that senses mitotic failure and responds by driving a cell to an irreversible antiproliferative fate of death or senescence. Thus, failed mitotic catastrophe can promote the unrestrained growth of defective cells, thereby representing a major gateway to tumour development. Furthermore, the activation of mitotic catastrophe offers significant therapeutic advantage which has been exploited in the action of conventional and targeted anticancer agents. Yet, despite its importance in tumour prevention and treatment, the molecular mechanism of mitotic catastrophe is not well understood. A better understanding of the signals that determine cell fate following failed or defective mitosis will reveal new opportunities to selectively target and enhance the programme for therapeutic benefit and reveal biomarkers to predict patient response. This review is focused on the molecular mechanism of mitotic catastrophe induction and signalling and highlights current strategies to exploit the process in cancer therapy.