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癌症中自噬的治疗靶向。第二部分:治疗诱导自噬的药理学调节。

Therapeutic targeting of autophagy in cancer. Part II: pharmacological modulation of treatment-induced autophagy.

机构信息

Department of Laboratory Medicine, Radboud university medical center, PO Box 9101, 6500 HB, Nijmegen, The Netherlands; Department of Radiation Oncology, Radboud university medical center, PO Box 9101, 6500 HB, Nijmegen, The Netherlands.

Department of Radiation Oncology, Radboud university medical center, PO Box 9101, 6500 HB, Nijmegen, The Netherlands.

出版信息

Semin Cancer Biol. 2015 Apr;31:99-105. doi: 10.1016/j.semcancer.2014.06.001. Epub 2014 Jun 14.

Abstract

Autophagy, the catabolic pathway in which cells recycle organelles and other parts of their own cytoplasm, is increasingly recognised as an important cytoprotective mechanism in cancer cells. Several cancer treatments stimulate the autophagic process and when autophagy is inhibited, cancer cells show an enhanced response to multiple treatments. These findings have nourished the theory that autophagy provides cancer cells with a survival advantage during stressful conditions, including exposure to therapeutics. Therefore, interference with the autophagic response can potentially enhance the efficacy of cancer therapy. In this review we examine two approaches to modulate autophagy as complementary cancer treatment: inhibition and induction. Inhibition of autophagy during cancer treatment eliminates its cytoprotective effects. Conversely, induction of autophagy combined with conventional cancer therapy exerts severe cytoplasmic degradation that can ultimately lead to cell death. We will discuss how autophagy can be therapeutically manipulated in cancer cells and how interactions between the conventional cancer therapies and autophagy modulation influence treatment outcome.

摘要

自噬是一种细胞内的分解代谢途径,可使细胞循环利用自身的细胞器和其他细胞质成分,它正日益被认为是癌细胞中的一种重要的细胞保护机制。一些癌症治疗方法会刺激自噬过程,而当自噬被抑制时,癌细胞对多种治疗方法的反应会增强。这些发现为这样一种理论提供了依据,即自噬在包括暴露于治疗药物在内的应激条件下为癌细胞提供了生存优势。因此,干扰自噬反应可能会增强癌症治疗的效果。在这篇综述中,我们探讨了两种调节自噬作为互补癌症治疗的方法:抑制和诱导。在癌症治疗过程中抑制自噬可以消除其细胞保护作用。相反,诱导自噬与常规癌症治疗相结合会导致严重的细胞质降解,最终可能导致细胞死亡。我们将讨论如何在癌细胞中对自噬进行治疗性操作,以及常规癌症治疗与自噬调节之间的相互作用如何影响治疗效果。

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