Pommier Y
Laboratory of Molecular Pharmacology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4225, USA.
Semin Oncol. 1996 Feb;23(1 Suppl 3):3-10.
Topoisomerase I enzymes are ubiquitous and play a pivotal role in DNA transcription, replication, and repair. The eukaryotic form of this enzyme is highly conserved and its inhibition leads to accumulation of DNA strand breaks ('cleavable complexes') and ultimately cell death. An understanding of the role of eukaryotic topoisomerase I has led researchers to identify this enzyme as a potential target for anticancer therapy. Indeed, topoisomerase I is inhibited by samptothecin (isolated from a plant extract), and derivatives of this agent are being developed with improved physicochemical and pharmacologic characteristics. These agents may provide a new dimension to chemotherapy through their novel mechanism of action.
拓扑异构酶I在DNA转录、复制和修复过程中普遍存在并发挥着关键作用。这种酶的真核形式高度保守，对其抑制会导致DNA链断裂（“可切割复合物”）的积累，最终导致细胞死亡。对真核拓扑异构酶I作用的了解促使研究人员将该酶确定为抗癌治疗的潜在靶点。实际上，拓扑异构酶I可被喜树碱（从植物提取物中分离得到）抑制，并且正在开发具有改善的物理化学和药理学特性的该药物的衍生物。这些药物可能通过其新颖的作用机制为化疗带来新的维度。
