DNA damage and repair dependencies of ionising radiation modalities.
DNA damage and repair dependencies of ionising radiation modalities.
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DOI：
10.1042/bsr20222586
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发表时间：
2023-10-31
影响因子：
4
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中科院分区：
文献类型：
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放射疗法用于治疗约50%的人类癌症，主要采用光子辐射。然而，粒子放射疗法由于更精确的剂量沉积和增加的线性能量转移（LET）而产生了优于常规光子的显著益处，所述线性能量转移（LET）产生增强的治疗反应。具体而言，质子束治疗（PBT）和碳离子放射治疗（CIRT）的特征在于布拉格峰，其产生低入射辐射剂量，其中大部分能量沉积被限定在可以特异性靶向肿瘤的小区域内，随后是低出射剂量。PBT被认为是相对低的LET，而CIRT是更密集的电离，因此高LET。尽管有放射治疗类型，但肿瘤细胞的杀伤在很大程度上依赖于DNA损伤的引入，DNA损伤破坏了肿瘤细胞的修复能力。众所周知，DNA损伤的复杂性随着LET的增加而增加，这导致生物学有效性的增强，尽管在不同辐射源后激活的特定DNA修复途径尚不清楚。需要这些知识来确定这些途径中的特定蛋白质和酶是否可以被靶向以进一步提高辐射的功效。在这篇综述中，我们提供了不同的辐射方式和DNA修复途径，这些响应的概述。我们还提供了研究LET和DNA损伤复杂性对DNA修复途径选择的影响的最新知识，随后提供了有关如何在治疗上利用这些途径中的酶来进一步提高肿瘤放射敏感性的证据，从而提高肿瘤的放射治疗敏感性。放疗功效。
Radiotherapy is utilised in the treatment of ∼50% of all human cancers, which predominantly employs photon radiation. However, particle radiotherapy elicits significant benefits over conventional photons due to more precise dose deposition and increased linear energy transfer (LET) that generates an enhanced therapeutic response. Specifically, proton beam therapy (PBT) and carbon ion radiotherapy (CIRT) are characterised by a Bragg peak, which generates a low entrance radiation dose, with the majority of the energy deposition being defined within a small region which can be specifically targeted to the tumour, followed by a low exit dose. PBT is deemed relatively low-LET whereas CIRT is more densely ionising and therefore high LET. Despite the radiotherapy type, tumour cell killing relies heavily on the introduction of DNA damage that overwhelms the repair capacity of the tumour cells. It is known that DNA damage complexity increases with LET that leads to enhanced biological effectiveness, although the specific DNA repair pathways that are activated following the different radiation sources is unclear. This knowledge is required to determine whether specific proteins and enzymes within these pathways can be targeted to further increase the efficacy of the radiation. In this review, we provide an overview of the different radiation modalities and the DNA repair pathways that are responsive to these. We also provide up-to-date knowledge of studies examining the impact of LET and DNA damage complexity on DNA repair pathway choice, followed by evidence on how enzymes within these pathways could potentially be therapeutically exploited to further increase tumour radiosensitivity, and therefore radiotherapy efficacy.