Vitti Eirini Terpsi, Parsons Jason L
Cancer Research Centre, Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool L3 9TA, UK.
Cancers (Basel). 2019 Jul 5;11(7):946. doi: 10.3390/cancers11070946.
Proton beam therapy (PBT) offers significant benefit over conventional (photon) radiotherapy for the treatment of a number of different human cancers, largely due to the physical characteristics. In particular, the low entrance dose and maximum energy deposition in depth at a well-defined region, the Bragg peak, can spare irradiation of proximal healthy tissues and organs at risk when compared to conventional radiotherapy using high-energy photons. However, there are still biological uncertainties reflected in the relative biological effectiveness that varies along the track of the proton beam as a consequence of the increases in linear energy transfer (LET). Furthermore, the spectrum of DNA damage induced by protons, particularly the generation of complex DNA damage (CDD) at high-LET regions of the distal edge of the Bragg peak, and the specific DNA repair pathways dependent on their repair are not entirely understood. This knowledge is essential in understanding the biological impact of protons on tumor cells, and ultimately in devising optimal therapeutic strategies employing PBT for greater clinical impact and patient benefit. Here, we provide an up-to-date review on the radiobiological effects of PBT versus photon radiotherapy in cells, particularly in the context of DNA damage. We also review the DNA repair pathways that are essential in the cellular response to PBT, with a specific focus on the signaling and processing of CDD induced by high-LET protons.
质子束疗法（PBT）在治疗多种不同的人类癌症方面比传统（光子）放射疗法具有显著优势，这主要归因于其物理特性。特别是，与使用高能光子的传统放射疗法相比，在明确界定的区域（布拉格峰）处低的入射剂量和深度处的最大能量沉积，可以使近端健康组织和危险器官免受照射。然而，由于线性能量传递（LET）增加，沿质子束轨迹的相对生物有效性仍存在生物学不确定性。此外，质子诱导的DNA损伤谱，特别是在布拉格峰远端高LET区域复杂DNA损伤（CDD）的产生，以及依赖于其修复的特定DNA修复途径尚未完全了解。这些知识对于理解质子对肿瘤细胞的生物学影响至关重要，最终对于设计采用PBT的最佳治疗策略以获得更大的临床效果和患者受益也至关重要。在此，我们提供了关于PBT与光子放射疗法在细胞中的放射生物学效应的最新综述，特别是在DNA损伤的背景下。我们还综述了细胞对PBT反应中至关重要的DNA修复途径，特别关注高LET质子诱导的CDD的信号传导和处理。
