Amaravadi Ravi K, Thompson Craig B
Abramson Cancer Center at the University of Pennsylvania, Philadelphia, PA 19104, USA.
Clin Cancer Res. 2007 Dec 15;13(24):7271-9. doi: 10.1158/1078-0432.CCR-07-1595.
Metabolic and therapeutic stresses activate several signal transduction pathways that regulate cell death and cell survival in cancer cells. Although decades of research unraveled the pathways that regulate apoptosis and allowed the development of novel diagnostic and therapeutic modalities in cancer treatment, only recently has the regulation and significance of tumor cell autophagy and necrosis become the focus of investigations. Necrosis is an irreversible inflammatory form of cell death. In contrast, autophagy is a reversible process that can contribute both to tumor cell death and survival. This review describes recent advances in understanding the regulation of autophagy and necrosis and their implications for cancer therapy. Currently available methods to measure autophagy and necrosis are highlighted. The effect of tumor cell autophagy and necrosis on host immunity is explored. Finally, therapeutic approaches that target autophagy and necrosis in cancer are described.
代谢应激和治疗应激会激活多种信号转导通路,这些通路可调节癌细胞的细胞死亡和细胞存活。尽管数十年的研究揭示了调节细胞凋亡的通路,并推动了癌症治疗中新型诊断和治疗方法的发展,但直到最近,肿瘤细胞自噬和坏死的调节及其意义才成为研究的焦点。坏死是一种不可逆的炎症性细胞死亡形式。相比之下,自噬是一个可逆的过程,它既可能导致肿瘤细胞死亡,也可能促进其存活。本文综述了在理解自噬和坏死调节及其对癌症治疗的影响方面的最新进展。重点介绍了目前可用的测量自噬和坏死的方法。探讨了肿瘤细胞自噬和坏死对宿主免疫的影响。最后,描述了针对癌症中自噬和坏死的治疗方法。