阻断自噬用于癌症治疗:综合综述。
Blockage of Autophagy for Cancer Therapy: A Comprehensive Review.
发表日期:2024 Jul 07
作者:
Ahmed Mostafa Ibrahim Abdelrahman Hassan, Yuxin Zhao, Xiuping Chen, Chengwei He
来源:
CLINICAL PHARMACOLOGY & THERAPEUTICS
摘要:
癌症的发病率和死亡率不断增加,使其成为全球死亡的主要原因。手术、放疗和化疗等传统治疗方法由于治疗耐药性而面临很大的局限性。自噬是一种细胞自我降解机制,在癌症发展、耐药性和治疗中发挥着至关重要的作用。这篇综述研究了自噬抑制作为癌症治疗策略的潜力。从 1967 年到 2024 年,我们对 Embase、PubMed 和 Google Scholar 数据库进行了系统检索,以识别自噬抑制剂及其在癌症治疗中的机制的研究。该综述包括利用体外和体内实验方法、文献综述和临床试验的原创文章。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”。氯喹 (CQ) 和羟氯喹 (HCQ) 等自噬抑制剂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了良好的前景。其他抑制剂如渥曼青霉素和 SAR405 则针对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,使癌细胞更容易受到细胞毒性药物的影响。涉及 CQ 和 HCQ 的临床试验已显示出令人鼓舞的结果,但需要进一步研究以优化它们在癌症治疗中的应用。自噬在癌症中发挥双重作用,既作为生存机制,又作为细胞死亡途径。针对自噬为癌症治疗提供了一种可行的策略,特别是与现有治疗相结合时。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且针对具体情况的治疗方法。
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.