How apoptosis is regulated, and what goes wrong in cancer
How apoptosis is regulated, and what goes wrong in cancer
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DOI：
10.1136/bmj.322.7301.1538
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发表时间：
2001-06-23
影响因子：
--
通讯作者：
Bergh, J
中科院分区：
文献类型：
--
作者：
Sjöström, J;Bergh, J
程序性细胞死亡(细胞凋亡)是胚胎发育和组织内稳态所需的进化保守途径。1细胞凋亡是对许多刺激的正常生理反应，包括不可修复的DNA损伤。各种疾病的发展是由于过度激活(神经退行性疾病、免疫缺陷、缺血再灌注损伤)或抑制程序性细胞死亡(癌症、自身免疫性疾病)。2在癌症中，增殖和程序性细胞死亡之间的平衡被破坏，而凋亡途径的缺陷使具有遗传异常的细胞得以存活。大多数细胞毒性和激素治疗，以及放射治疗，最终都会导致无法修复的细胞损伤，从而引发细胞凋亡，从而最终杀死癌细胞。因此，癌症治疗的效果不仅取决于它们造成的细胞损伤，还取决于细胞通过诱导凋亡机制对损伤做出反应的能力。因此，凋亡途径的突变可能会导致对药物和辐射的抗药性。这种突变可能作为化疗耐药的预测因子，最重要的是，可能成为新的治疗靶点。线粒体和细胞表面受体是细胞凋亡的两条主要途径。1线粒体途径被认为在癌症治疗中起重要作用，并由bcl2家族蛋白介导。细胞死亡的最终执行是由caspase级联反应完成的，这是由线粒体释放细胞色素C触发的。
Programmed cell death (apoptosis) is an evolutionarily conserved pathway needed for embryonic development and tissue homoeostasis. 1 Apoptosis is the normal physiological response to many stimuli, including irreparable DNA damage. Various diseases evolve because of hyperactivation (neurodegenerative diseases, immunodeficiency, ischaemia-reperfusion injury) or suppression of programmed cell death (cancer, autoimmune disorders). 2 In cancer, the balance between proliferation and programmed cell death is disturbed, and defects in apoptotic pathways allow cells with genetic abnormalities to survive. Most cytotoxic and hormonal treatments, as well as radiation, ultimately kill cancer cells by causing irreparable cellular damage that triggers apoptosis. Consequently, the efficacy of cancer treatments depends not only on the cellular damage they cause but also on the cell’s ability to respond to the damage by inducing apoptotic machinery. Accordingly, mutations in apoptotic pathways may result in resistance to drugs and radiation. Such mutations might serve as predictors of chemoresistance and, most importantly, as new treatment targets. Mitochondria and cell surface receptors mediate the two main pathways of apoptosis. 1 The mitochondrial pathway is thought to be important in response to cancer treatment and is mediated by bcl-2 family proteins. The final execution of cell death is performed by the caspase cascade, which is triggered by release of cytochrome C from mitochondria.