State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao SAR 999078, China.
Department of Pharmaceutical Science, Faculty of Health Sciences, University of Macau, Taipa, Macao SAR 999078, China.
Int J Mol Sci. 2024 Jul 7;25(13):7459. doi: 10.3390/ijms25137459.
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.
癌症的发病率和死亡率不断上升，使其成为全球主要的死亡原因。由于治疗耐药性，手术、放疗和化疗等传统治疗方法面临着重大的局限性。自噬是一种细胞自我降解的机制，在癌症的发展、耐药性和治疗中起着至关重要的作用。本综述探讨了自噬抑制作为癌症治疗策略的潜力。我们对 Embase、PubMed 和 Google Scholar 数据库进行了系统检索，检索时间为 1967 年至 2024 年，以确定关于自噬抑制剂及其在癌症治疗中的机制的研究。本综述包括使用体外和体内实验方法的原始文章、文献综述和临床试验。使用的关键词为“Autophagy”“Inhibitors”“Molecular mechanism”“Cancer therapy”和“Clinical trials”。自噬抑制剂，如氯喹（CQ）和羟氯喹（HCQ），通过抑制溶酶体酸化和阻止自噬体降解，在临床前研究中显示出了一定的潜力。其他抑制剂，如渥曼青霉素和 SAR405，靶向自噬途径的特定成分。将这些抑制剂与化疗联合使用已证明具有增强的疗效，使癌细胞对细胞毒性药物更敏感。涉及 CQ 和 HCQ 的临床试验已经取得了令人鼓舞的结果，尽管需要进一步的研究来优化它们在癌症治疗中的应用。自噬在癌症中具有双重作用，既是一种生存机制，也是一种细胞死亡途径。靶向自噬为癌症治疗提供了一种可行的策略，特别是当与现有的治疗方法结合使用时。然而，自噬调节的复杂性和潜在的副作用需要进一步的研究，以开发精确和特定于背景的治疗方法。
