Division of Genomic Stability and DNA Repair, Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
Genes Dev. 2011 Oct 1;25(19):1999-2010. doi: 10.1101/gad.17558811.
Macroautophagy (referred to hereafter as autophagy) is a highly regulated cellular process that serves to remove damaged proteins and organelles from the cell. Autophagy contributes to an array of normal and pathological processes, and has recently emerged as a key regulator of multiple aspects of cancer biology. The role of autophagy in cancer is complex and is likely dependent on tumor type, stage, and genetic context. This complexity is illustrated by the identification of settings where autophagy acts potently to either promote or inhibit tumorigenesis. In this review, I discuss the underlying basis for these opposing functions and propose a model suggesting a dynamic role for autophagy in malignancy. Collectively, the data point to autophagy as serving as a barrier to limit tumor initiation. Once neoplastic lesions are established, it appears that adaptive changes occur that now result in positive roles for autophagy in malignant progression and in subsequent tumor maintenance. Remarkably, constitutive activation of autophagy is critical for continued growth of some tumors, serving to both reduce oxidative stress and provide key intermediates to sustain cell metabolism. Autophagy is also induced in response to cancer therapies where it can function as a survival mechanism that limits drug efficacy. These findings have inspired significant interest in applying anti-autophagy therapies as an entirely new approach to cancer treatment. It is now apparent that aberrant control of autophagy is among the key hallmarks of cancer. While much needs to be learned about the regulation and context-dependent biological functions of autophagy, it seems clear that modulation of this process will be an attractive avenue for future cancer therapeutic approaches.
自噬（ hereafter 后简称自噬）是一种高度调控的细胞过程，有助于从细胞中清除受损的蛋白质和细胞器。自噬有助于一系列正常和病理过程，并且最近已成为癌症生物学多个方面的关键调节剂。自噬在癌症中的作用是复杂的，并且可能取决于肿瘤类型、阶段和遗传背景。自噬在促进或抑制肿瘤发生方面具有强大作用的情况下，这种复杂性得到了体现。在这篇综述中，我讨论了这些相反功能的基础，并提出了一个模型，表明自噬在恶性肿瘤中具有动态作用。总的来说，这些数据表明自噬作为限制肿瘤起始的屏障。一旦肿瘤病变建立，似乎会发生适应性变化，现在自噬在恶性进展和随后的肿瘤维持中具有积极作用。值得注意的是，自噬的组成性激活对于一些肿瘤的持续生长至关重要，它既能减轻氧化应激，又能提供维持细胞代谢的关键中间产物。自噬也会对癌症治疗产生反应，在这种情况下，它可以作为一种生存机制，限制药物的疗效。这些发现激发了人们对应用抗自噬疗法作为一种全新的癌症治疗方法的极大兴趣。现在很明显，自噬的异常控制是癌症的关键标志之一。尽管需要了解自噬的调节和上下文相关的生物学功能，但似乎很清楚，调节这个过程将是未来癌症治疗方法的一个有吸引力的途径。
