肿瘤细胞治疗研究
英文原题：Emerging therapies for glioblastoma.
胶质母细胞瘤（GBM）仍与不良预后相关，即使采用最大范围安全切除、放疗和替莫唑胺治疗，中位生存期仍为15-18个月。
胶质母细胞瘤（GBM）仍与不良预后相关，尽管采用最大范围安全切除、放疗和替莫唑胺治疗，中位生存期仍为15-18个月。治疗开发日益聚焦于克服耐药性、瘤内异质性以及跨血脑屏障递送受限的问题。靶向治疗的进展包括对EGFR抑制剂、多靶点酪氨酸激酶抑制剂和FGFR导向药物的评估，而BRAF V600E和NTRK融合等罕见的分子定义亚群则提供了肿瘤不可知论的精准治疗途径。JAK/STAT抑制、PARP阻断和PI3K/AKT/mTOR通路调控仍在研究中，尽管临床获益并不一致。与此同时，整合多组学分析、患者来源类器官和功能性药物检测的精准肿瘤学平台正在优化治疗选择并支持合理的药物联合方案。GBM AGILE和INSIGhT等适应性临床试验框架正在加速在分层队列中评估新型药物，而ChemoID指导治疗、放射基因组学分析和数字建模等新兴方法正开始影响转化终点。免疫治疗仍是一个活跃的研究领域，但迄今为止疗效有限。免疫检查点抑制剂作为单药治疗尚未显示出显著的生存获益，但与疫苗、溶瘤病毒和工程化细胞疗法的联合策略正在评估中。CAR T细胞疗法正朝着双特异性和装甲化构建体方向发展，并采用局部区域递送，而DNX-2401和PVSRIPO等溶瘤病毒在部分患者中显示出持久缓解的潜力。展望未来，进展可能来自基于生物标志物的多模式方案，这些方案整合靶向药物、下一代免疫疗法和精准导向策略，同时将转化终点纳入试验设计，以应对GBM复杂的生物学特性和治疗耐药性。
Glioblastoma (GBM) remains associated with poor outcomes, with a median survival of 15-18 months despite maximal safe resection, radiotherapy, and temozolomide. Therapeutic development has increasingly centered on overcoming drug resistance, intratumoral diversity, and restricted delivery across the blood-brain barrier. Progress in targeted therapy includes evaluation of EGFR inhibitors, multitarget tyrosine kinase inhibitors, and FGFR-directed agents, while rare molecularly defined subsets such as BRAF V600E and NTRK fusions offer tumor-agnostic precision approaches. JAK/STAT inhibition, PARP blockade, and PI3K/AKT/mTOR pathway modulation remain under investigation, although clinical benefit has been inconsistent. In parallel, precision oncology platforms incorporating multi-omic profiling, patient-derived organoids, and functional drug testing are refining therapy selection and supporting rational drug combinations. Adaptive clinical trial frameworks such as GBM AGILE and INSIGhT are accelerating the evaluation of novel agents within stratified cohorts,while emerging approaches including ChemoID-guided therapy, radiogenomic profiling, and digital modeling are beginning to influence translational endpoints. Immunotherapy continues to be an active area of research, though efficacy has thus far been limited. Immune checkpoint inhibitors have not yet demonstrated significant survival benefits as monotherapy, but combination strategies with vaccines, oncolytic viruses, and engineered cellular therapies are under evaluation. CAR T-cell therapies are advancing toward bispecific and armored constructs with locoregional delivery, while oncolytic viruses such as DNX-2401 and PVSRIPO demonstrate potential for durable responses in select patients. Looking ahead, progress is likely to arise from biomarker-informed, multimodal regimens that integrate targeted agents, next-generation immunotherapies, and precision-guided strategies, while embedding translational endpoints into trial design to address the complex biology and therapeutic resistance of GBM.
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