Autophagy is intricately linked with many intracellular signaling pathways, particularly nutrient-sensing mechanisms and cell death signaling cascades. In cancer, the roles of autophagy are context dependent. Tumor cell–intrinsic effects of autophagy can be both tumor suppressive and tumor promotional. Autophagy can therefore not only activate and inhibit cell death, but also facilitate the switch between cell death mechanisms. Moreover, autophagy can play opposing roles in the tumor microenvironment via non–cell-autonomous mechanisms. Preclinical data support a tumor-promotional role of autophagy in established tumors and during cancer therapy; this has led to the launch of dozens of clinical trials targeting autophagy in multiple cancer types. However, many questions remain: which tumors and genetic backgrounds are the most sensitive to autophagy inhibition, and which therapies should be combined with autophagy inhibitors? Additionally, since cancer cells are under selective pressure and are prone to adaptation, particularly after treatment, it is unclear if and how cells adapt to autophagy inhibition. Here we review recent literature addressing these issues.

中文翻译：

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自噬和癌症：细胞死亡途径的调节和癌细胞适应

自噬与许多细胞内信号传导途径错综复杂地联系在一起，特别是营养感应机制和细胞死亡信号级联。在癌症中，自噬的作用是依赖于环境的。肿瘤细胞自噬的内在作用既可以抑制肿瘤，也可以促进肿瘤。因此，自噬不仅可以激活和抑制细胞死亡，还可以促进细胞死亡机制之间的转换。此外，自噬可以通过非细胞自主机制在肿瘤微环境中发挥相反的作用。临床前数据支持自噬在已形成的肿瘤和癌症治疗过程中具有促进肿瘤的作用；这导致了数十项针对多种癌症类型的自噬的临床试验的启动。然而，仍然存在许多问题：哪些肿瘤和遗传背景对自噬抑制最敏感，哪些疗法应与自噬抑制剂联合使用？此外，由于癌细胞处于选择压力下并且易于适应，特别是在治疗后，因此尚不清楚细胞是否以及如何适应自噬抑制。在这里，我们回顾了最近解决这些问题的文献。