节拍化疗（MC），即长期连续施用抗癌药物，作为传统最大耐受剂量（MTD）化疗的替代方案而受到关注。通过将 MC 与其他治疗方法相结合，可以增强治疗效果，同时最大限度地减少毒性。 MC 采用多种机制，使其成为对抗各种癌症的通用方法。然而，耐药性限制了 MC 的长期有效性，因此需要不断开发抗癌药物。由于目标蛋白识别、虚拟筛选、先导化合物优化以及安全性和有效性评估等过程，传统的药物发现过程漫长且成本高昂。药物再利用 (DR) 筛选 FDA 批准的药物的新用途，正在成为一种具有成本效益的替代方案。采用实验和计算方法，例如蛋白质结合测定、体外细胞毒性测试、基于结构的筛选和几种类型的关联分析（基于相似性、基于网络和目标基因）以及回顾性临床分析用于虚拟筛选。本综述涵盖了 MC 的机制、其在各种癌症中的应用、DR 策略、重新利用药物的示例以及相关挑战和未来方向。© 2024。作者获得波兰科学院药理学研究所的独家许可。

Metronomic chemotherapy (MC), long-term continuous administration of anticancer drugs, is gaining attention as an alternative to the traditional maximum tolerated dose (MTD) chemotherapy. By combining MC with other treatments, the therapeutic efficacy is enhanced while minimizing toxicity. MC employs multiple mechanisms, making it a versatile approach against various cancers. However, drug resistance limits the long-term effectiveness of MC, necessitating ongoing development of anticancer drugs. Traditional drug discovery is lengthy and costly due to processes like target protein identification, virtual screening, lead optimization, and safety and efficacy evaluations. Drug repurposing (DR), which screens FDA-approved drugs for new uses, is emerging as a cost-effective alternative. Both experimental and computational methods, such as protein binding assays, in vitro cytotoxicity tests, structure-based screening, and several types of association analyses (Similarity-Based, Network-Based, and Target Gene), along with retrospective clinical analyses, are employed for virtual screening. This review covers the mechanisms of MC, its application in various cancers, DR strategies, examples of repurposed drugs, and the associated challenges and future directions.© 2024. The Author(s) under exclusive licence to Maj Institute of Pharmacology Polish Academy of Sciences.