Autophagy: In the cROSshairs of cancer.
Autophagy: In the cROSshairs of cancer.
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DOI：
10.1016/j.bcp.2016.10.006
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发表时间：
2017-02-15
影响因子：
5.8
通讯作者：
Ghosh R
中科院分区：
文献类型：
--
作者：
Hambright HG;Ghosh R
肿瘤的两个突出特征是氧化还原破坏或氧化应激表型，以及高自噬信号，使这两种现象成为理想的治疗靶点。然而，氧化还原破坏与自噬信号传导之间的关系尚未得到很好的表征，而产生活性氧（ROS）的化疗药物对自噬的临床影响值得立即关注，因为自噬在很大程度上导致了化疗耐药。在这篇评论中，我们将重点放在黑色素瘤上，以其为例，为当前文献中关于自噬和氧化还原信号的作用提供清晰的解释，这些作用适用于大多数肿瘤类型的发生和维持。此外，我们讨论了在药物干预和细胞命运决定过程中ROS和自噬信号之间的串扰。我们试图阐明自噬在临床前和临床环境中使用ros生成剂治疗后调节细胞命运的作用，并讨论自噬在细胞命运决定和细胞死亡机制中的新作用。我们还讨论了实验设计和数据解释中氧化还原和自噬评估的技术方面。最后，我们提出了一个具有争议性的观点，即临床相关性，氧化还原和自噬双重靶向治疗途径的新挑战，以及未来需要解决的方向，以推进该领域的基础和转化方面。
Two prominent features of tumors that contribute to oncogenic survival signaling are redox disruption, or oxidative stress phenotype, and high autophagy signaling, making both phenomena ideal therapeutic targets. However, the relationship between redox disruption and autophagy signaling is not well characterized and the clinical impact of reactive oxygen species (ROS)-generating chemotherapeutics on autophagy merits immediate attention as autophagy largely contributes to chemotherapeutic resistance. In this commentary we focus on melanoma, using it as an example to provide clarity to current literature regarding the roles of autophagy and redox signaling which can be applicable to initiation and maintenance of most tumor types. Further, we address the crosstalk between ROS and autophagy signaling during pharmacological intervention and cell fate decisions. We attempt to elucidate the role of autophagy in regulating cell fate following treatment with ROS-generating agents in preclinical and clinical settings and discuss the emerging role of autophagy in cell fate decisions and as a cell death mechanism. We also address technical aspects of redox and autophagy evaluation in experimental design and data interpretation. Lastly, we present a provocative view of the clinical relevance, emerging challenges in dual targeting of redox and autophagy pathways for therapy, and the future directions to be addressed in order to advance both basic and translational aspects of this field.