Dysregulation of apoptotic signaling in cancer: molecular mechanisms and therapeutic opportunities.
Dysregulation of apoptotic signaling in cancer: molecular mechanisms and therapeutic opportunities.
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DOI：
10.1002/jcb.21707
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发表时间：
2008-07-01
影响因子：
4
通讯作者：
Khosravi-Far, Roya
中科院分区：
文献类型：
--
作者：
Plati, Jessica;Bucur, Octavian;Khosravi-Far, Roya
细胞凋亡是一种受到严格调控的细胞自杀程序，通过消除不必要或有害的细胞，在维持组织稳态中发挥重要作用。这种天然防御机制的缺陷会促进恶性转化，并经常赋予转化细胞化学抗性。事实上，细胞凋亡的逃避已被认为是癌症的标志。鉴于多种机制在多个层面上发挥作用来协调细胞凋亡的调节，细胞复杂的信号网络中存在大量细胞凋亡失调的机会。已经阐明了保护癌细胞免于凋亡的几种分子机制。这些进展促进了新型细胞凋亡诱导剂的开发，这些药物已证明对各种类型的癌细胞和/或对传统细胞毒性疗法具有耐药性的癌细胞具有单药活性。在此，我们将重点介绍癌症中发现的细胞凋亡失调的几种主要模式。我们还将讨论几种旨在重建细胞凋亡反应的治疗策略，从而根除癌细胞，包括那些对传统疗法表现出耐药性的癌细胞。
Apoptosis is a tightly regulated cell suicide program that plays an essential role in the maintenance of tissue homeostasis by eliminating unnecessary or harmful cells. Defects in this native defense mechanism promote malignant transformation and frequently confer chemoresistance to transformed cells. Indeed, the evasion of apoptosis has been recognized as a hallmark of cancer. Given that multiple mechanisms function at many levels to orchestrate the regulation of apoptosis, a multitude of opportunities for apoptotic dysregulation are present within the intricate signaling network of cell. Several of the molecular mechanisms by which cancer cells are protected from apoptosis have been elucidated. These advances have facilitated the development of novel apoptosis-inducing agents that have demonstrated single-agent activity against various types of cancers cells and/or sensitized resistant cancer cells to conventional cytotoxic therapies. Herein, we will highlight several of the central modes of apoptotic dysregulation found in cancer. We will also discuss several therapeutic strategies that aim to reestablish the apoptotic response, and thereby eradicate cancer cells, including those that demonstrate resistance to traditional therapies.
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