Cancer therapy in the necroptosis era.
Cancer therapy in the necroptosis era.
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坏死性凋亡时代的癌症治疗
DOI：
10.1038/cdd.2016.8
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发表时间：
2016-05
影响因子：
12.4
通讯作者：
Chen Y
中科院分区：
文献类型：
--
作者：
Su Z;Yang Z;Xie L;DeWitt JP;Chen Y
坏死性凋亡是由受体相互作用蛋白激酶1（RIP1）、RIP3和混合谱系激酶结构域样蛋白（MLKL）执行的一种不依赖半胱天冬酶的调节性细胞死亡形式。近年来，基于坏死性凋亡的肿瘤治疗被认为是一种新的抗肿瘤治疗策略。然而，这种类型的治疗是否可行或只是一个概念模型存在很大的争议。支持者认为，由于坏死性凋亡和细胞凋亡使用不同的分子途径，触发坏死性凋亡可能是根除抗凋亡癌细胞的另一种方法。这一假说已被最近的研究所初步证实。然而，一些怀疑论者怀疑这种策略，因为在许多癌细胞中观察到的坏死性凋亡机制的内在或后天缺陷。此外，另外两个问题是坏死性凋亡诱导剂是否选择性地杀死癌细胞而不干扰正常细胞，以及它是否会导致炎性疾病。本文综述了目前围绕这一争议的基于坏死性凋亡的抗肿瘤研究，并讨论了这种新疗法的优势，潜在的问题和对策。
Necroptosis is a caspase-independent form of regulated cell death executed by the receptor-interacting protein kinase 1 (RIP1), RIP3, and mixed lineage kinase domain-like protein (MLKL). Recently, necroptosis-based cancer therapy has been proposed to be a novel strategy for antitumor treatment. However, a big controversy exists on whether this type of therapy is feasible or just a conceptual model. Proponents believe that because necroptosis and apoptosis use distinct molecular pathways, triggering necroptosis could be an alternative way to eradicate apoptosis-resistant cancer cells. This hypothesis has been preliminarily validated by recent studies. However, some skeptics doubt this strategy because of the intrinsic or acquired defects of necroptotic machinery observed in many cancer cells. Moreover, two other concerns are whether or not necroptosis inducers are selective in killing cancer cells without disturbing the normal cells and whether it will lead to inflammatory diseases. In this review, we summarize current studies surrounding this controversy on necroptosis-based antitumor research and discuss the advantages, potential issues, and countermeasures of this novel therapy.