Department of Surgery, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Synthetic Nanobiotechnology and Biomachines, Synthetic Biology and Precision Medicine Centre, NextGeneration Health Cluster, Council for Scientific and Industrial Research, Pretoria, South Africa.
Adv Exp Med Biol. 2023;1410:115-126. doi: 10.1007/5584_2022_744.
Drug resistance in leukaemia is a major problem that needs to be addressed. Precision medicine provides an avenue to reduce drug resistance through a personalised treatment plan. It has helped to better stratify patients based on their molecular profile and therefore improved the sensitivity of patients to a given therapeutic regimen. However, therapeutic options are still limited for patients who have already been subjected to many lines of chemotherapy. The process of designing and developing new drugs requires significant resources, including money and time. Drug repurposing has been explored as an alternative to identify effective drug(s) that could be used to target leukaemia and lessen the burden of drug resistance. The drug repurposing process usually includes preclinical studies with drug screening and clinical trials before approval. Although most of the repurposed drugs that have been identified are generally safe for leukaemia treatment, they seem not to be good candidates for monotherapy but could have value in combination with other drugs, especially for patients who have exhausted therapeutic options. In this review, we highlight precision medicine in leukaemia and the role of drug repurposing. Specifically, we discuss the several screening methods via chemoinformatic, in vitro, and ex vivo that have facilitated and accelerated the drug repurposing process.
白血病耐药是一个亟待解决的问题。精准医学提供了一条通过个体化治疗方案来降低耐药性的途径。它有助于根据患者的分子特征更好地对患者进行分层，从而提高患者对特定治疗方案的敏感性。然而，对于已经接受过多线化疗的患者，治疗选择仍然有限。设计和开发新药的过程需要大量的资源，包括资金和时间。药物重定位已被探索作为一种替代方法，以确定可用于靶向白血病和减轻耐药性负担的有效药物。药物重定位过程通常包括药物筛选的临床前研究和批准前的临床试验。尽管大多数已确定的再利用药物通常对白血病治疗是安全的，但它们似乎不是单药治疗的理想选择，但在与其他药物联合使用时可能具有价值，特别是对于已经用尽治疗选择的患者。在这篇综述中，我们强调了白血病精准医学和药物重定位的作用。具体来说，我们讨论了通过化学信息学、体外和离体等几种筛选方法，这些方法促进和加速了药物重定位过程。
