Radiotherapy is one of the main cancer treatments being used for ~50% of all cancer patients. Conventional radiotherapy typically utilises X-rays (photons); however, there is increasing use of particle beam therapy (PBT), such as protons and carbon ions. This is because PBT elicits significant benefits through more precise dose delivery to the cancer than X-rays, but also due to the increases in linear energy transfer (LET) that lead to more enhanced biological effectiveness. Despite the radiotherapy type, the introduction of DNA damage ultimately drives the therapeutic response through stimulating cancer cell death. To combat this, cells harbour cell cycle checkpoints that enables time for efficient DNA damage repair. Interestingly, cancer cells frequently have mutations in key genes such as TP53 and ATM that drive the G1/S checkpoint, whereas the G2/M checkpoint driven through ATR, Chk1 and Wee1 remains intact. Therefore, targeting the G2/M checkpoint through specific inhibitors is considered an important strategy for enhancing the efficacy of radiotherapy. In this review, we focus on inhibitors of Chk1 and Wee1 kinases and present the current biological evidence supporting their utility as radiosensitisers with different radiotherapy modalities, as well as clinical trials that have and are investigating their potential for cancer patient benefit.
放射治疗是约50%癌症患者采用的主要治疗手段之一。传统放疗通常使用X射线（光子），但粒子束治疗（如质子和碳离子）的应用日益广泛。这是因为相较于X射线，粒子束治疗能通过更精确的剂量投射带来显著优势，同时其更高的线性能量转移（LET）可产生更强的生物效应。无论采用何种放疗方式，DNA损伤的诱导最终通过刺激癌细胞死亡驱动治疗反应。为应对DNA损伤，细胞通过细胞周期检查点机制为高效修复争取时间。值得注意的是，癌细胞常在TP53、ATM等驱动G1/S检查点的关键基因中存在突变，而由ATR、Chk1和Wee1调控的G2/M检查点通常保持完整。因此，通过特异性抑制剂靶向G2/M检查点被认为是增强放疗疗效的重要策略。本综述聚焦于Chk1和Wee1激酶抑制剂，系统阐述其作为不同放疗模式放射增敏剂的生物学证据，并对已完成及正在进行的相关临床试验进行评述，以探讨其在改善癌症患者预后方面的潜力。
肿瘤(癌症)患者之家