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PARP 抑制剂药物在乳腺癌、卵巢癌、前列腺癌和胰腺癌治疗中的应用:临床试验更新。

PARP Inhibitor Drugs in the Treatment of Breast, Ovarian, Prostate and Pancreatic Cancers: An Update of Clinical Trials.

机构信息

Department of Medical Oncology, Cancer Center of Southeastern Ontario, Queen's University, Kingston, Ontario K7L 3N6, Canada.

Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario K7L 3N6, Canada.

出版信息

Curr Drug Targets. 2018;19(1):21-37. doi: 10.2174/1389450118666170711151518.

Abstract

BACKGROUND

PARP inhibitors appear to offer a promising role in the accompaniment of many of the cytotoxic agents used in the present day to combat cancer proliferation in BRCA ½ deficient tumors. Current species of PARP inhibitors have yet to demonstrate a superior effect to that of existing therapies when administered as a single agent; however, they have appeared to amplify the effect of these existing chemotherapies when utilized together. This suggests that PARP inhibitors could play an effective maintenance role in current cancer-combating strategies. In the immediate future, PARP inhibitors may only be applicable to a select group of cancers (i.e., those caused by defective HR pathways), though research is emerging that could indicate an extension of applicability to HR proficient cancer types as well. For the time being, however, the current literature suggests that a viable PARP inhibitorchemotherapy hybrid targeting HR deficient cancers could be well on its way very soon.

OBJECTIVE

In this manuscript we explores the ongoing and the completed clinical trials for different PARP inhibitors.

CONCLUSION

Since the approval of Olaparib by both FDA and EMA, further clinical trials continue to investigate the use of Olaparib and other PARP inhibitors. The anticipating outcome of these trials may clarify the benefit of PARP inhibitors in management of various BRCA mutated solid tumors.

摘要

背景

PARP 抑制剂似乎在伴随许多目前用于对抗 BRCA ½ 缺陷肿瘤中癌症增殖的细胞毒性药物方面发挥了有希望的作用。目前的 PARP 抑制剂在作为单一药物给药时尚未显示出优于现有疗法的效果;但是,当它们一起使用时,它们似乎增强了这些现有化疗药物的效果。这表明 PARP 抑制剂可以在当前的癌症治疗策略中发挥有效的维持作用。在不久的将来,PARP 抑制剂可能仅适用于一组特定的癌症(即由缺陷 HR 途径引起的癌症),尽管正在出现的研究可能表明将其适用性扩展到 HR 有效的癌症类型。但是,目前的文献表明,针对 HR 缺陷癌症的可行 PARP 抑制剂化疗混合物可能很快就会出现。

目的

在本文中,我们探讨了不同 PARP 抑制剂的正在进行和已完成的临床试验。

结论

自 FDA 和 EMA 批准奥拉帕利以来,进一步的临床试验继续研究奥拉帕利和其他 PARP 抑制剂的用途。这些试验的预期结果可能会阐明 PARP 抑制剂在管理各种 BRCA 突变型实体瘤中的益处。

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