Regulated cell death pathways: new twists in modulation of BCL2 family function.
Regulated cell death pathways: new twists in modulation of BCL2 family function.
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DOI：
10.1158/1535-7163.mct-08-0895
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发表时间：
2009-06
影响因子：
5.7
通讯作者：
Lu B
中科院分区：
文献类型：
--
作者：
Sasi N;Hwang M;Jaboin J;Csiki I;Lu B
许多细胞死亡途径已被确认。虽然细胞凋亡和自噬已经有了很好的特征，但程序性坏死最近受到了关注，并可能为抑制耐药肿瘤提供临床选择。坏死的主要特征是大范围渗透、肿胀、细胞膜破裂和促炎细胞因子的释放。传统上，癌细胞坏死预示着预后不良，因为慢性炎症被发现会促进肿瘤生长。然而，许多与坏死相关的抗肿瘤作用已在某些情况下被发现，例如形成有效的抗肿瘤免疫反应。通过这种方式，寻找方法来减弱坏死的促肿瘤作用，同时通过药物、放疗和致敏来参与抗肿瘤途径，这可能是未来的临床重点。我们假设使用Bcl-2抑制剂可能会增强以炎症和抗肿瘤免疫为特征的坏死死亡。在这篇文章中，我们简要地回顾了细胞凋亡和自噬，并解释了为什么坏死可能是一个合适的替代治疗终点。然后，我们强调新的Bcl-2抑制剂可能在未来为我们的假设提供临床应用。
A number of cell death pathways have been recognized. Though apoptosis and autophagy have been well characterized, programmed necrosis has recently received attention and may provide clinical alternatives to suppress resistant tumors. Necrosis is primarily characterized by large-scale permeabilization, swelling, and rupture of cell membranes and the release of pro-inflammatory cytokines. Traditionally, necrosis in cancer cells has been indicative of poor prognoses, as chronic inflammation was found to encourage tumor growth. Yet, many antitumor effects associated with necrosis have been discovered in certain settings, such as the formation of an effective antitumor immune response. In this way, finding ways to attenuate the pro-tumor effects of necrosis while engaging the antitumor pathways via drugs, radiation, and sensitization may prove valuable as a clinical focus for the future. We hypothesize that the use of Bcl-2 inhibitors may enhance necrotic death characterized by inflammation and antitumor immunity. In this article, we briefly review apoptosis and autophagy and reason how necrosis may be a suitable alternative therapeutic endpoint. We then highlight novel inhibitors of Bcl-2 that may provide clinical application of our hypothesis in the future.