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胶质瘤中的 DNA 双链断裂修复:分子参与者和治疗策略。

The DNA Double-Strand Break Repair in Glioma: Molecular Players and Therapeutic Strategies.

机构信息

Experimental Therapeutics and Molecular Imaging Unit, Department of Neurology, Neuro-Oncology Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA.

出版信息

Mol Neurobiol. 2022 Sep;59(9):5326-5365. doi: 10.1007/s12035-022-02915-2. Epub 2022 Jun 13.

Abstract

Gliomas are the most frequent type of tumor in the central nervous system, which exhibit properties that make their treatment difficult, such as cellular infiltration, heterogeneity, and the presence of stem-like cells responsible for tumor recurrence. The response of this type of tumor to chemoradiotherapy is poor, possibly due to a higher repair activity of the genetic material, among other causes. The DNA double-strand breaks are an important type of lesion to the genetic material, which have the potential to trigger processes of cell death or cause gene aberrations that could promote tumorigenesis. This review describes how the different cellular elements regulate the formation of DNA double-strand breaks and their repair in gliomas, discussing the therapeutic potential of the induction of this type of lesion and the suppression of its repair as a control mechanism of brain tumorigenesis.

摘要

神经胶质瘤是中枢神经系统中最常见的肿瘤类型,具有使其治疗变得困难的特性,例如细胞浸润、异质性和负责肿瘤复发的干细胞样细胞的存在。这种肿瘤对化疗和放疗的反应不佳,这可能是由于遗传物质的更高修复活性等原因造成的。DNA 双链断裂是遗传物质的一种重要损伤类型,它有可能引发细胞死亡过程或导致可能促进肿瘤发生的基因突变。这篇综述描述了不同的细胞成分如何调节神经胶质瘤中 DNA 双链断裂的形成及其修复,讨论了诱导这种损伤和抑制其修复作为脑肿瘤发生的控制机制的治疗潜力。

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