Kozalak Gül, Koşar Ali
Faculty of Engineering and Natural Science, Sabancı University, Istanbul 34956, Turkey.
Center of Excellence for Functional Surfaces and Interfaces for Nano Diagnostics (EFSUN), Sabancı University, Istanbul 34956, Turkey.
Cancer Drug Resist. 2023 Dec 25;6:838-857. doi: 10.20517/cdr.2023.108. eCollection 2023.
Multiple myeloma (MM) is a type of hematological cancer that occurs when B cells become malignant. Various drugs such as proteasome inhibitors, immunomodulators, and compounds that cause DNA damage can be used in the treatment of MM. Autophagy, a type 2 cell death mechanism, plays a crucial role in determining the fate of B cells, either promoting their survival or inducing cell death. Therefore, autophagy can either facilitate the progression or hinder the treatment of MM disease. In this review, autophagy mechanisms that may be effective in MM cells were covered and evaluated within the contexts of unfolded protein response (UPR), bone marrow microenvironment (BMME), drug resistance, hypoxia, DNA repair and transcriptional regulation, and apoptosis. The genes that are effective in each mechanism and research efforts on this subject were discussed in detail. Signaling pathways targeted by new drugs to benefit from autophagy in MM disease were covered. The efficacy of drugs that regulate autophagy in MM was examined, and clinical trials on this subject were included. Consequently, among the autophagy mechanisms that are effective in MM, the most suitable ones to be used in the treatment were expressed. The importance of 3D models and microfluidic systems for the discovery of new drugs for autophagy and personalized treatment was emphasized. Ultimately, this review aims to provide a comprehensive overview of MM disease, encompassing autophagy mechanisms, drugs, clinical studies, and further studies.
多发性骨髓瘤(MM)是一种血液系统癌症,发生于B细胞恶变时。多种药物如蛋白酶体抑制剂、免疫调节剂以及导致DNA损伤的化合物可用于治疗MM。自噬作为一种2型细胞死亡机制,在决定B细胞命运方面起着关键作用,既可以促进其存活,也可以诱导细胞死亡。因此,自噬既可以促进MM疾病的进展,也可以阻碍其治疗。在这篇综述中,在未折叠蛋白反应(UPR)、骨髓微环境(BMME)、耐药性、缺氧、DNA修复和转录调控以及细胞凋亡的背景下,涵盖并评估了可能对MM细胞有效的自噬机制。详细讨论了每种机制中起作用的基因以及关于该主题的研究工作。介绍了在MM疾病中从自噬中获益的新药所靶向的信号通路。研究了调节MM中自噬的药物的疗效,并纳入了关于该主题的临床试验。因此,在对MM有效的自噬机制中,表达了最适合用于治疗的机制。强调了3D模型和微流控系统在发现自噬新药和个性化治疗方面的重要性。最终,这篇综述旨在全面概述MM疾病,包括自噬机制、药物、临床研究及进一步研究。