Department of Pathology, College of Korean Medicine, Kyung Hee University, 1-5 Hoegidong Dongdaemun-gu, Seoul 02447, Republic of Korea.
Korean Medicine-Based Drug Repositioning Cancer Research Center, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea.
Cells. 2023 Jan 31;12(3):458. doi: 10.3390/cells12030458.
Recent evidence suggests that autophagy is a governed catabolic framework enabling the recycling of nutrients from injured organelles and other cellular constituents via a lysosomal breakdown. This mechanism has been associated with the development of various pathologic conditions, including cancer and neurological disorders; however, recently updated studies have indicated that autophagy plays a dual role in cancer, acting as a cytoprotective or cytotoxic mechanism. Numerous preclinical and clinical investigations have shown that inhibiting autophagy enhances an anticancer medicine's effectiveness in various malignancies. Autophagy antagonists, including chloroquine and hydroxychloroquine, have previously been authorized in clinical trials, encouraging the development of medication-combination therapies targeting the autophagic processes for cancer. In this review, we provide an update on the recent research examining the anticancer efficacy of combining drugs that activate cytoprotective autophagy with autophagy inhibitors. Additionally, we highlight the difficulties and progress toward using cytoprotective autophagy targeting as a cancer treatment strategy. Importantly, we must enable the use of suitable autophagy inhibitors and coadministration delivery systems in conjunction with anticancer agents. Therefore, this review briefly summarizes the general molecular process behind autophagy and its bifunctional role that is important in cancer suppression and in encouraging tumor growth and resistance to chemotherapy and metastasis regulation. We then emphasize how autophagy and cancer cells interacting with one another is a promising therapeutic target in cancer treatment.
最近的证据表明,自噬是一种受调控的分解代谢框架,能够通过溶酶体分解从受损细胞器和其他细胞成分中回收营养物质。这种机制与各种病理状况的发展有关,包括癌症和神经紊乱;然而,最近更新的研究表明,自噬在癌症中发挥双重作用,作为一种细胞保护或细胞毒性机制。大量的临床前和临床研究表明,抑制自噬可以提高各种恶性肿瘤中抗癌药物的疗效。自噬拮抗剂,包括氯喹和羟氯喹,以前已经在临床试验中获得批准,这鼓励了针对自噬过程的联合药物治疗癌症的药物组合疗法的发展。在这篇综述中,我们提供了最新的研究进展,这些研究检查了联合使用激活细胞保护自噬的药物和自噬抑制剂的抗癌功效。此外,我们还强调了将细胞保护自噬靶向作为癌症治疗策略的困难和进展。重要的是,我们必须能够使用合适的自噬抑制剂和联合抗癌药物的共给药系统。因此,这篇综述简要总结了自噬的一般分子过程及其在癌症抑制以及促进肿瘤生长、对化疗耐药和转移调节中的双重作用。然后,我们强调了自噬和癌细胞之间的相互作用是癌症治疗中一个有前途的治疗靶点。