Chin Lynn, Kumana Cyrus R, Kwong Yok-Lam, Gill Harinder
Department of Medicine, School of Clinical Medicine, University of Hong Kong, Hong Kong 999077, China.
Pharmaceutics. 2022 Sep 14;14(9):1945. doi: 10.3390/pharmaceutics14091945.
Appreciation of the properties of arsenic trioxide (ATO) has redefined the treatment landscape for acute promyelocytic leukaemia (APL) and offers promise as a treatment for numerous other diseases. The benefits of ATO in patients with APL is related to its ability to counteract the effects of PML::RARA, an oncoprotein that is invariably detected in the blood or bone marrow of affected individuals. The PML::RARA oncoprotein is degraded specifically by binding to ATO. Thus ATO, in combination with all-trans retinoic acid, has become the curative treatment for ATO. The multiple mechanisms of action of ATO has also paved the way for application in various condition encompassing autoimmune or inflammatory disorders, solid organ tumours, lymphomas and other subtypes of AML. The development of oral formulation of ATO (oral ATO) has reduced costs of treatment and improved treatment convenience allowing widespread applicability. In this review, we discuss the mechanisms of action of ATO, the development of oral ATO, and the applications of oral ATO in APL and other diseases.
对三氧化二砷(ATO)特性的认识重新定义了急性早幼粒细胞白血病(APL)的治疗格局,并有望用于治疗许多其他疾病。ATO对APL患者的益处与其抵消PML::RARA影响的能力有关,PML::RARA是一种癌蛋白,在受影响个体的血液或骨髓中总是可以检测到。PML::RARA癌蛋白通过与ATO结合而被特异性降解。因此,ATO与全反式维甲酸联合使用已成为APL的治愈性疗法。ATO的多种作用机制也为其在包括自身免疫或炎症性疾病、实体器官肿瘤、淋巴瘤和其他急性髓系白血病亚型在内的各种病症中的应用铺平了道路。ATO口服制剂(口服ATO)的开发降低了治疗成本,提高了治疗便利性,使其具有广泛的适用性。在这篇综述中,我们讨论了ATO的作用机制、口服ATO的开发以及口服ATO在APL和其他疾病中的应用。