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组蛋白去乙酰化酶抑制剂与放射治疗的作用机制序列:概述

Mechanistic Sequence of Histone Deacetylase Inhibitors and Radiation Treatment: An Overview.

作者信息

Seane Elsie Neo, Nair Shankari, Vandevoorde Charlot, Joubert Anna

机构信息

Department of Radiography, School of Health Care Sciences, Faculty of Health Sciences, University of Pretoria, Pretoria 0028, South Africa.

Department of Medical Imaging and Therapeutic Sciences, Faculty of Health and Wellness, Cape Peninsula University of Technology, Cape Town 7530, South Africa.

出版信息

Pharmaceuticals (Basel). 2024 May 8;17(5):602. doi: 10.3390/ph17050602.

Abstract

Histone deacetylases inhibitors (HDACis) have shown promising therapeutic outcomes in haematological malignancies such as leukaemia, multiple myeloma, and lymphoma, with disappointing results in solid tumours when used as monotherapy. As a result, combination therapies either with radiation or other deoxyribonucleic acid (DNA) damaging agents have been suggested as ideal strategy to improve their efficacy in solid tumours. Numerous in vitro and in vivo studies have demonstrated that HDACis can sensitise malignant cells to both electromagnetic and particle types of radiation by inhibiting DNA damage repair. Although the radiosensitising ability of HDACis has been reported as early as the 1990s, the mechanisms of radiosensitisation are yet to be fully understood. This review brings forth the various protocols used to sequence the administration of radiation and HDACi treatments in the different studies. The possible contribution of these various protocols to the ambiguity that surrounds the mechanisms of radiosensitisation is also highlighted.

摘要

组蛋白去乙酰化酶抑制剂(HDACis)在白血病、多发性骨髓瘤和淋巴瘤等血液系统恶性肿瘤中已显示出有前景的治疗效果,但作为单一疗法用于实体瘤时结果令人失望。因此,与放疗或其他脱氧核糖核酸(DNA)损伤剂联合治疗被认为是提高其在实体瘤中疗效的理想策略。大量的体外和体内研究表明,HDACis可通过抑制DNA损伤修复使恶性细胞对电磁辐射和粒子辐射均敏感。尽管HDACis的放射增敏能力早在20世纪90年代就已被报道,但其放射增敏机制尚未完全明确。本综述提出了不同研究中用于安排放疗和HDACi治疗给药顺序的各种方案。还强调了这些不同方案对围绕放射增敏机制的模糊性可能产生的影响。

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