Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
Nat Rev Clin Oncol. 2011 May 17;8(9):528-39. doi: 10.1038/nrclinonc.2011.71.
Autophagy is an important homeostatic cellular recycling mechanism responsible for degrading unnecessary or dysfunctional cellular organelles and proteins in all living cells. Autophagy is particularly active during metabolic stress. In the cancer cell it fulfils a dual role, having tumor-promoting and tumor-suppressing properties. Functional autophagy prevents necrosis and inflammation, which can lead to genetic instability. On the other hand, autophagy might be important for tumor progression by providing energy through its recycling mechanism during unfavorable metabolic circumstances. A central checkpoint that negatively regulates autophagy is mTOR, and anticancer drugs inhibiting the PI3K/Akt/mTOR axis putatively stimulate autophagy. However, whether autophagy contributes to the antitumor effect of these drugs or to drug resistance is largely unknown. The antimalarial drugs chloroquine and hydroxychloroquine inhibit autophagy, leading to increased cytotoxicity in combination with several anticancer drugs in preclinical models. The therapeutic clinical roles of autophagy induction and inhibition remain to be defined. To improve our understanding of autophagy in human cancers new methods for measuring autophagy in clinical samples need to be developed. This Review delineates the possible role of autophagy as a novel target for anticancer therapy.
自噬是一种重要的细胞内稳态回收机制，负责降解所有活细胞中不必要或功能失调的细胞细胞器和蛋白质。自噬在代谢应激期间特别活跃。在癌细胞中，它具有双重作用，具有促进肿瘤和抑制肿瘤的特性。功能正常的自噬可防止坏死和炎症，从而导致遗传不稳定性。另一方面，自噬可能通过在不利的代谢环境中通过其回收机制提供能量，对肿瘤进展很重要。负调节自噬的中央检查点是 mTOR，抑制 PI3K/Akt/mTOR 轴的抗癌药物可能会刺激自噬。然而，自噬是否有助于这些药物的抗肿瘤作用或耐药性在很大程度上尚不清楚。抗疟药物氯喹和羟氯喹抑制自噬，在临床前模型中与几种抗癌药物联合使用时会导致细胞毒性增加。自噬诱导和抑制的治疗临床作用仍有待确定。为了提高我们对人类癌症中自噬的理解，需要开发用于测量临床样本中自噬的新方法。这篇综述阐述了自噬作为一种新的抗癌治疗靶点的可能作用。
