Punshon Leah D, Fabbrizi Maria Rita, Phoenix Ben, Green Stuart, Parsons Jason L
Department of Cancer and Genomic Sciences, College of Medicine and Health, University of Birmingham, Birmingham B15 2TT, UK.
School of Physics and Astronomy, University of Birmingham, Birmingham B15 2TT, UK.
Cells. 2024 Dec 13;13(24):2065. doi: 10.3390/cells13242065.
Photon (X-ray) radiotherapy is the most common treatment used in cancer therapy. However, the exposure of normal tissues and organs at risk to ionising radiation often results in a significant incidence of low-grade adverse side effects, whilst high-grade toxicities also occur at concerningly high rates. As an alternative, boron neutron capture therapy (BNCT) aims to create densely ionising helium and lithium ions directly within cancer cells, thus sparing the surrounding normal cells and tissues but also leading to significantly more effective tumour control than X-rays. Although very promising for patients with recurring and highly invasive tumours, BNCT does not currently have widespread use worldwide, in part due to limited and reliable neutron sources for clinical use. Another limitation is devising strategies leading to the selective and optimal accumulation of boron within the cancer cells. Boronophenylalanine (BPA) is currently the major compound used in BNCT which takes advantage of the amino acid transporter LAT1 that is overexpressed in a number of human cancers. Additionally, there is a lack of in-depth knowledge regarding the impact of BNCT on cellular DNA, and the molecular mechanisms that are responsive to the treatment, which are important in developing optimal therapeutic strategies using BNCT, are unclear. In this review, we highlight the current knowledge of the radiobiology of BNCT acquired from in vitro and in vivo studies, particularly in the context of DNA damage and repair, but also present evidence of established and new boron-containing compounds aimed at enhancing the specificity and effectiveness of the treatment.
光子（X射线）放射疗法是癌症治疗中最常用的治疗方法。然而，正常组织和器官暴露于电离辐射往往会导致低级别不良副作用的发生率显著增加，同时高级别毒性的发生率也高得令人担忧。作为一种替代方法，硼中子俘获疗法（BNCT）旨在直接在癌细胞内产生密集电离的氦离子和锂离子，从而使周围的正常细胞和组织免受辐射，而且与X射线相比，对肿瘤的控制效果显著更好。尽管BNCT对复发性和高侵袭性肿瘤患者非常有前景，但目前在全球范围内尚未广泛应用，部分原因是临床可用的中子源有限且不可靠。另一个限制是设计能使硼在癌细胞内选择性和最佳积累的策略。硼苯丙氨酸（BPA）是目前BNCT中使用的主要化合物，它利用了在多种人类癌症中过度表达的氨基酸转运体LAT1。此外，关于BNCT对细胞DNA的影响以及对治疗有反应的分子机制，我们缺乏深入了解，而这些对于制定使用BNCT 的最佳治疗策略很重要，目前尚不清楚。在这篇综述中，我们重点介绍了从体外和体内研究中获得的关于BNCT放射生物学的当前知识，特别是在DNA损伤和修复方面，同时还展示了已有的和新型含硼化合物的证据，这些化合物旨在提高治疗的特异性和有效性。
