PDF(Pubmed)
Abstract：
The incidence and mortality of cancer are increasing, making it a leading cause of death worldwide. Conventional treatments such as surgery, radiotherapy, and chemotherapy face significant limitations due to therapeutic resistance. Autophagy, a cellular self-degradation mechanism, plays a crucial role in cancer development, drug resistance, and treatment. This review investigates the potential of autophagy inhibition as a therapeutic strategy for cancer. A systematic search was conducted on Embase, PubMed, and Google Scholar databases from 1967 to 2024 to identify studies on autophagy inhibitors and their mechanisms in cancer therapy. The review includes original articles utilizing in vitro and in vivo experimental methods, literature reviews, and clinical trials. Key terms used were \"Autophagy\", \"Inhibitors\", \"Molecular mechanism\", \"Cancer therapy\", and \"Clinical trials\". Autophagy inhibitors such as chloroquine (CQ) and hydroxychloroquine (HCQ) have shown promise in preclinical studies by inhibiting lysosomal acidification and preventing autophagosome degradation. Other inhibitors like wortmannin and SAR405 target specific components of the autophagy pathway. Combining these inhibitors with chemotherapy has demonstrated enhanced efficacy, making cancer cells more susceptible to cytotoxic agents. Clinical trials involving CQ and HCQ have shown encouraging results, although further investigation is needed to optimize their use in cancer therapy. Autophagy exhibits a dual role in cancer, functioning as both a survival mechanism and a cell death pathway. Targeting autophagy presents a viable strategy for cancer therapy, particularly when integrated with existing treatments. However, the complexity of autophagy regulation and the potential side effects necessitate further research to develop precise and context-specific therapeutic approaches.
摘要：
癌症的发病率和死亡率都在增加，使其成为全球死亡的主要原因。常规治疗如手术，放射治疗,和化疗面临显著的局限性，由于治疗抗性。自噬,细胞自我降解机制，在癌症的发展中起着至关重要的作用，耐药性,和治疗。这篇综述研究了自噬抑制作为癌症治疗策略的潜力。在Embase上进行了系统搜索,PubMed,和谷歌学者数据库从1967年到2024年，以确定自噬抑制剂及其在癌症治疗中的机制的研究。这篇综述包括利用体外和体内实验方法的原创文章，文献综述，和临床试验。使用的关键术语是“自噬”，“抑制剂”，“分子机制”，“癌症治疗”，和“临床试验”。自噬抑制剂如氯喹（CQ）和羟氯喹（HCQ）通过抑制溶酶体酸化和防止自噬体降解在临床前研究中显示出希望。其他抑制剂，如wortmannin和SAR405靶向自噬途径的特定成分。将这些抑制剂与化疗结合使用已证明疗效增强，使癌细胞对细胞毒性剂更敏感。涉及CQ和HCQ的临床试验显示出令人鼓舞的结果，尽管需要进一步的研究来优化它们在癌症治疗中的应用。自噬在癌症中表现出双重作用，作为生存机制和细胞死亡途径。靶向自噬是癌症治疗的可行策略，特别是当与现有的治疗相结合。然而,自噬调节的复杂性和潜在的副作用需要进一步研究以开发精确和特定于环境的治疗方法.
