Combining PARP Inhibition with Platinum, Ruthenium or Gold Complexes for Cancer Therapy.,ChemMedChem

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Combining PARP Inhibition with Platinum, Ruthenium or Gold Complexes for Cancer Therapy.
ChemMedChem ( IF 3.6 ) Pub Date : 2020-08-19 , DOI: 10.1002/cmdc.202000391
Nur Aininie Yusoh ₁ , Haslina Ahmad _{1,

2} , Martin R Gill ₃

Affiliation

Platinum drugs are heavily used first‐line chemotherapeutic agents for many solid tumours and have stimulated substantial interest in the biological activity of DNA‐binding metal complexes. These complexes generate DNA lesions which trigger the activation of DNA damage response (DDR) pathways that are essential to maintain genomic integrity. Cancer cells exploit this intrinsic DNA repair network to counteract many types of chemotherapies. Now, advances in the molecular biology of cancer has paved the way for the combination of DDR inhibitors such as poly (ADP‐ribose) polymerase (PARP) inhibitors (PARPi) and agents that induce high levels of DNA replication stress or single‐strand break damage for synergistic cancer cell killing. In this review, we summarise early‐stage, preclinical and clinical findings exploring platinum and emerging ruthenium anti‐cancer complexes alongside PARPi in combination therapy for cancer and also describe emerging work on the ability of ruthenium and gold complexes to directly inhibit PARP activity.

中文翻译：

将 PARP 抑制与铂、钌或金络合物相结合进行癌症治疗。

铂类药物是许多实体瘤广泛使用的一线化疗药物，并激发了人们对 DNA 结合金属复合物的生物活性的浓厚兴趣。这些复合物产生 DNA 损伤，从而触发 DNA 损伤反应 (DDR) 途径的激活，这对于维持基因组完整性至关重要。癌细胞利用这种内在的 DNA 修复网络来对抗多种化疗。现在，癌症分子生物学的进步为 DDR 抑制剂（例如聚（ADP-核糖）聚合酶（PARP）抑制剂（PARPi））与诱导高水平 DNA 复制应激或单链断裂的药物的组合铺平了道路协同杀死癌细胞的损伤。在这篇综述中，我们总结了探索铂和新兴钌抗癌复合物与 PARPi 联合用于癌症联合治疗的早期、临床前和临床研究结果，并描述了关于钌和金复合物直接抑制 PARP 活性的能力的最新研究。

更新日期：2020-08-19

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