肿瘤细胞治疗研究
英文原题：Glioblastoma treatment slowly moves toward change: novel druggable targets and translational horizons in 2022.
胶质母细胞瘤（GBM）的分子异质性和脑解剖学特征严重制约药物有效性。
引言：胶质母细胞瘤（GBM）是成人最常见的原发性脑肿瘤。过去30年来，GBM治疗选择基本未变；尽管采用积极的多模式治疗，生存期仅略有延长。随着对GBM生物学认识逐渐深入，并对其基因组特征进行全面分析，研究者揭示了GBM的异质性，推动了更有效的分子分类和创新靶向治疗方法的开发。综述范围：本文报告免疫治疗和靶向治疗领域值得关注的创新，并介绍试验设计的当前进展，包括免疫肿瘤药物联合方案及靶点组合。专家观点：GBM的分子异质性和脑部解剖特征严重限制药物疗效。尽管如此，GBM的创新治疗策略为未来研究和药物开发带来启示，例如多特异性“现货型”CAR-T疗法、溶瘤病毒疗法和自体树突状细胞疫苗。靶向治疗临床试验结果令人失望，主要源于信号通路与生物过程之间复杂的相互作用导致耐药；因此，未来必须开发联合策略和多模式疗法。
INTRODUCTION: Glioblastoma (GBM) is the most common primary brain tumor in adults. GBM treatment options have been the same for the past 30 years and have only modestly extended survival, despite aggressive multimodal treatments. The progressively better knowledge of GBM biology and a comprehensive analysis of its genomic profile have elucidated GBM heterogeneity, contributing to a more effective molecular classification and to the development of innovative targeted therapeutic approaches. AREAS COVERED: This article reports all the noteworthy innovations for immunotherapy and targeted therapy, providing insights into the current advances in trial designs, including combination therapies with immuno-oncology agents and target combinations. EXPERT OPINION: GBM molecular heterogeneity and brain anatomical characteristics critically restrain drug effectiveness. Nevertheless, stimulating insights for future research and drug development come from innovative treatment strategies for GBM, such as multi-specific 'off-the-shelf' CAR-T therapy, oncolytic viral therapy and autologous dendritic cell vaccination. Disappointing results from targeted therapies-clinical trials are mainly due to complex interferences between signaling pathways and biological processes leading to drug resistance: hence, it is imperative in the future to develop combinatorial approaches and multimodal therapies.
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