Division of Pediatric Hematology/Oncology, Children's Hospital of Michigan, Detroit, MI, USA; Discipline of Pediatrics, Central Michigan University, Mt. Pleasant, MI, USA.
Cancer Biology Graduate Program, Wayne State University School of Medicine, Detroit, MI, USA; MD/PhD Program, Wayne State University School of Medicine, Detroit, MI, USA.
Biochem Pharmacol. 2023 Jul;213:115630. doi: 10.1016/j.bcp.2023.115630. Epub 2023 May 30.
For many centuries, products of natural origin from plants, marine, microbes and soil micro-organisms have been studied by numerous researchers across the world to yield many of the chemotherapeutic agents we use in this modern era. There has been a tremendous gain in knowledge from various screening and separating techniques which led to the discovery of biologically active small molecules from natural products. Preclinical studies testing the antitumor activities of these agents against tumor cell lines and xenograft animal models were the gateway to the clinical trials in humans leading to the approval of these agents that are in clinical use today. This review summarizes how various chemotherapeutic agents were discovered from products of natural origin, their preclinical development, and their indications in both pediatric and adult oncology. Many of these natural products have contributed to the very high cure rates of both pediatric leukemias and solid tumors.
几个世纪以来,来自植物、海洋、微生物和土壤微生物的天然产物一直被世界各地的众多研究人员研究,以产生我们在现代使用的许多化疗药物。各种筛选和分离技术带来了巨大的知识增长,从而从天然产物中发现了具有生物活性的小分子。对这些药物针对肿瘤细胞系和异种移植动物模型的抗肿瘤活性进行的临床前研究是进入人体临床试验的门户,导致了这些目前在临床使用的药物的批准。这篇综述总结了如何从天然产物中发现各种化疗药物,它们的临床前开发,以及它们在儿科和成人肿瘤学中的适应症。这些天然产物中的许多都为儿科白血病和实体瘤的高治愈率做出了贡献。