CELL INTELLIGENCE · 肿瘤细胞治疗研究

Glioblastoma (GBM) is the most aggressive primary brain cancer, characterized by profound molecular and cellular heterogeneity, which contributes to its resistance to conventional therapies and poor prognosis. Despite multimodal treatments including surgical resection, radiation, and chemotherapy, median survival remains approximately 15 months. Recent advances in molecular and genetic profiling have elucidated key genetic alterations and molecular subtypes of GBM, such as EGFR amplification, PTEN and ATRX loss, and TP53 alterations, which have significant prognostic and therapeutic implications. These discoveries have spurred the development of targeted therapies aimed at disrupting aberrant signaling pathways like RTK/RAS/PI3K and TP53. However, treatment resistance remains a formidable challenge, driven by tumor heterogeneity, the complex tumor microenvironment (TME), and intrinsic adaptive mechanisms. Emerging therapeutic approaches aim to address these challenges, including the use of immunotherapies such as immune checkpoint inhibitors and CAR T-cell therapies, which target specific tumor antigens but face hurdles due to the immunosuppressive TME. Additionally, novel strategies like biopolymer-based interstitial therapies, focused ultrasound for blood-brain barrier disruption, and nanoparticle-based drug delivery systems show promise in enhancing the efficacy and precision of GBM treatments. This review explores the evolving landscape of GBM therapy, emphasizing the importance of personalized medicine through molecular profiling, the potential of combination therapies, and the need for innovative approaches to overcome therapeutic resistance. Continued research into GBM's biology and treatment modalities offers hope for improving patient outcomes.