URBC-NARILIS, University of Namur-FUNDP, 61 rue de Bruxelles, Namur, Belgium.
Biochem Pharmacol. 2011 Sep 1;82(5):427-34. doi: 10.1016/j.bcp.2011.06.015. Epub 2011 Jun 16.
Since the 1940s, chemotherapy has been the treatment of choice for metastatic disease. Chemotherapeutic agents target proliferating cells, inducing cell death. For most of the history of chemotherapy, apoptosis was thought to be the only mechanism of drug-induced cell death. More recently, a second type of cell death pathway has emerged: autophagy, also called type II programmed cell death. Autophagy is a tightly regulated process by which selected components of a cell are degraded. It primarily functions as a cell survival adaptive mechanism during stress conditions. However, persistent stress can also promote extensive autophagy, leading to cell death, hence its name. Alterations in the autophagy pathway have been described in cancer cells that suggest a tumor-suppressive function in early tumorigenesis, but a tumor-promoting function in established tumors. Moreover, accumulating data indicate a role for autophagy in chemotherapy-induced cancer cell death. Here, we discuss some of the evidence showing autophagy-dependent cell death induced by anti-neoplastic agents in different cancer models. On the other hand, in some other examples, autophagy dampens treatment efficacy, hence providing a therapeutic target to enhance cancer cell killing. In this paper, we propose a putative mechanism that could reconcile these two opposite observations.
自 20 世纪 40 年代以来，化疗一直是转移性疾病的首选治疗方法。化疗药物靶向增殖细胞，诱导细胞死亡。在化疗的大部分历史中，细胞凋亡被认为是药物诱导细胞死亡的唯一机制。最近，第二种细胞死亡途径出现了：自噬，也称为 II 型程序性细胞死亡。自噬是一种受严格调控的过程，通过该过程可以降解细胞的某些选定成分。它主要作为一种细胞在应激条件下的生存适应机制发挥作用。然而，持续的应激也会促进广泛的自噬，导致细胞死亡，因此得名。在癌细胞中已经描述了自噬途径的改变，提示其在早期肿瘤发生中具有肿瘤抑制功能，但在已建立的肿瘤中具有肿瘤促进功能。此外，越来越多的证据表明自噬在化疗诱导的癌细胞死亡中起作用。在这里，我们讨论了一些证据，表明在不同的癌症模型中，抗肿瘤药物诱导的自噬依赖性细胞死亡。另一方面，在其他一些例子中，自噬会降低治疗效果，因此为增强癌细胞杀伤提供了一个治疗靶点。在本文中，我们提出了一个假设机制，可以调和这两种相反的观察结果。
