Department of Pharmacology, University of California San Diego, La Jolla, CA, 92093, USA; Institutional Research Academic Career Development Award Program, University of California San Diego, La Jolla, CA, 92093, USA.
Molecular Therapeutics Program, Karmanos Cancer Institute, Detroit, MI, 48201, USA; Department of Oncology, Wayne State University, Detroit, MI, 48201, USA.
Cancer Lett. 2024 Nov 28;605:217285. doi: 10.1016/j.canlet.2024.217285. Epub 2024 Oct 10.
Autophagy is an intracellular degradation process that sequesters cytoplasmic components in double-membrane vesicles known as autophagosomes, which are degraded upon fusion with lysosomes. This pathway maintains the integrity of proteins and organelles while providing energy and nutrients to cells, particularly under nutrient deprivation. Deregulation of autophagy can cause genomic instability, low protein quality, and DNA damage, all of which can contribute to cancer. Autophagy can also be overactivated in cancer cells to aid in cancer cell survival and drug resistance. Emerging evidence indicates that autophagy has functions beyond cargo degradation, including roles in tumor immunity and cancer stem cell survival. Additionally, autophagy can also influence the tumor microenvironment. This feature warrants further investigation of the role of autophagy in cancer, in which autophagy manipulation can improve cancer therapies, including cancer immunotherapy. This review discusses recent findings on the regulation of autophagy and its role in cancer therapy and drug resistance.
自噬是一种细胞内降解过程，它将细胞质成分隔离在双层囊泡中，称为自噬体，自噬体与溶酶体融合后被降解。这条途径在提供细胞能量和营养的同时，保持蛋白质和细胞器的完整性，尤其是在营养缺乏的情况下。自噬的失调会导致基因组不稳定、蛋白质质量低下和 DNA 损伤，所有这些都会导致癌症。自噬也可以在癌细胞中过度激活，以帮助癌细胞存活和耐药。新出现的证据表明，自噬除了具有货物降解功能外，还具有在肿瘤免疫和癌症干细胞存活中的作用。此外，自噬还可以影响肿瘤微环境。这一特性需要进一步研究自噬在癌症中的作用，通过自噬的操纵可以改善癌症治疗，包括癌症免疫治疗。本文讨论了自噬的调节及其在癌症治疗和耐药性中的作用的最新发现。
