PDF(Pubmed)
Abstract：
Glioblastoma (GB), a prevalent and highly malignant primary brain tumour with a very high mortality rate due to its resistance to conventional therapies and invasive nature, resulting in 5-year survival rates of only 4-17%. Despite recent advancements in cancer management, the survival rates for GB patients have not significantly improved over the last 10-20 years. Consequently, there exists a critical unmet need for innovative therapies. One promising approach for GB is Targeted Alpha Therapy (TAT), which aims to selectively deliver potentially therapeutic radiation doses to malignant cells and the tumour microenvironment while minimising radiation exposure to surrounding normal tissue with or without conventional external beam radiation. This approach has shown promise in both pre-clinical and clinical settings. A review was conducted following PRISMA 2020 guidelines across Medline, SCOPUS, and Embase, identifying 34 relevant studies out of 526 initially found. In pre-clinical studies, TAT demonstrated high binding specificity to targeted GB cells, with affinity rates between 60.0% and 84.2%, and minimal binding to non-targeted cells (4.0-5.6%). This specificity significantly enhanced cytotoxic effects and improved biodistribution when delivered intratumorally. Mice treated with TAT showed markedly higher median survival rates compared to control groups. In clinical trials, TAT applied to recurrent GB (rGB) displayed varying success rates in extending overall survival (OS) and progression-free survival. Particularly effective when integrated into treatment regimens for both newly diagnosed and recurrent cases, TAT increased the median OS by 16.1% in newly diagnosed GB and by 36.4% in rGB, compared to current standard therapies. Furthermore, it was generally well tolerated with minimal adverse effects. These findings underscore the potential of TAT as a viable therapeutic option in the management of GB.
摘要：
胶质母细胞瘤(GB),一种普遍且高度恶性的原发性脑肿瘤，由于其对常规疗法的抵抗力和侵袭性，死亡率很高，导致5年生存率仅为4-17%。尽管最近在癌症管理方面取得了进展，在过去的10-20年中,GB患者的生存率没有显著改善.因此,对创新疗法存在关键的未满足需求。GB的一种有希望的方法是靶向α疗法(TAT)，其旨在选择性地将潜在治疗性放射剂量递送至恶性细胞和肿瘤微环境,同时在有或没有常规外部束放射的情况下最小化对周围正常组织的放射暴露。这种方法在临床前和临床环境中均显示出希望。根据Medline的PRISMA2020指南进行了审查，Scopus,和Embase,在最初发现的526项研究中，确定了34项相关研究。在临床前研究中,TAT表现出对靶向GB细胞的高结合特异性，亲和力在60.0%至84.2%之间，与非靶细胞的结合最小（4.0-5.6％）。当瘤内递送时,这种特异性显著增强细胞毒性作用并改善生物分布。与对照组相比,用TAT处理的小鼠显示显著更高的中位存活率。在临床试验中,应用于复发性GB（rGB）的TAT在延长总生存期（OS）和无进展生存期方面显示出不同的成功率。当纳入新诊断和复发病例的治疗方案时特别有效，TAT在新诊断的GB中增加了16.1%的中位OS，在rGB中增加了36.4%，与目前的标准疗法相比。此外，一般耐受性良好,不良反应最小.这些发现强调了TAT作为GB管理中可行的治疗选择的潜力。
