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组蛋白去乙酰化酶作为铂耐药上皮性卵巢癌的新治疗靶点

Histone deacetylases as new therapy targets for platinum-resistant epithelial ovarian cancer.

作者信息

Pchejetski Dmitri, Alfraidi Albandri, Sacco Keith, Alshaker Heba, Muhammad Aun, Monzon Leonardo

机构信息

School of Medicine, University of East Anglia, Bob Champion Research and Education Bldg 2.53, Norwich, UK.

Department of Surgery and Cancer, Hammersmith Hospital, Imperial College London, 1st Floor ICTEM, Du Cane Road, London, W12 0NN, UK.

出版信息

J Cancer Res Clin Oncol. 2016 Aug;142(8):1659-71. doi: 10.1007/s00432-015-2064-5. Epub 2015 Nov 11.

Abstract

INTRODUCTION

In developed countries, ovarian cancer is the fourth most common cancer in women. Due to the non-specific symptomatology associated with the disease many patients with ovarian cancer are diagnosed late, which leads to significantly poorer prognosis. Apart from surgery and radiotherapy, a substantial number of ovarian cancer patients will undergo chemotherapy and platinum based agents are the mainstream first-line therapy for this disease. Despite the initial efficacy of these therapies, many women relapse; therefore, strategies for second-line therapies are required. Regulation of DNA transcription is crucial for tumour progression, metastasis and chemoresistance which offers potential for novel drug targets.

METHODS

We have reviewed the existing literature on the role of histone deacetylases, nuclear enzymes regulating gene transcription.

RESULTS AND CONCLUSION

Analysis of available data suggests that a signifant proportion of drug resistance stems from abberant gene expression, therefore HDAC inhibitors are amongst the most promising therapeutic targets for cancer treatment. Together with genetic testing, they may have a potential to serve as base for patient-adapted therapies.

摘要

引言

在发达国家,卵巢癌是女性中第四大常见癌症。由于该疾病相关症状不具有特异性,许多卵巢癌患者确诊时已处于晚期,这导致预后明显较差。除手术和放疗外,大量卵巢癌患者将接受化疗,铂类药物是该疾病的主流一线治疗方案。尽管这些疗法初期有效,但许多女性会复发;因此,需要二线治疗策略。DNA转录调控对于肿瘤进展、转移和化疗耐药性至关重要,这为新型药物靶点提供了潜力。

方法

我们回顾了关于组蛋白脱乙酰酶(调节基因转录的核酶)作用的现有文献。

结果与结论

对现有数据的分析表明,相当一部分耐药性源于基因表达异常,因此组蛋白脱乙酰酶抑制剂是癌症治疗中最有前景的治疗靶点之一。与基因检测一起,它们可能有潜力作为个体化治疗的基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a632/11819375/c5bfa1b27ffa/432_2015_2064_Fig1_HTML.jpg

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