Sathgen Therapeutics, Godavari Biorefineries Limited, Somaiya Group Company, Mumbai, India.
Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Mumbai, India.
Drug Dev Res. 2024 Nov;85(7):e22261. doi: 10.1002/ddr.22261.
Glioblastoma multiforme (GBM) remains one of the most aggressive and lethal forms of brain cancer, characterized by rapid growth and resistance to conventional therapies. The present review explores the latest advancements in targeted therapies for GBM, emphasizing the critical role of the blood-brain barrier (BBB), blood-brain-tumor barrier, tumor microenvironment, and genetic mutations in influencing treatment outcomes. The impact of the key hallmarks of GBM, for example, chemoresistance, hypoxia, and the presence of glioma stem cells on the disease progression and multidrug resistance are discussed in detail. The major focus is on the innovative strategies aimed at overcoming these challenges, such as the use of monoclonal antibodies, small-molecule inhibitors, and novel drug delivery systems designed to enhance drug penetration across the BBB. Additionally, the potential of immunotherapy, specifically immune checkpoint inhibitors and vaccine-based approaches, to improve patient prognosis was explored. Recent clinical trials and preclinical studies are reviewed to provide a comprehensive overview of the current landscape and future prospects in GBM treatment. The integration of advanced computational models and personalized medicine approaches is also considered, aiming to tailor therapies to individual patient profiles for better efficacy. Overall, while significant progress has been made in understanding and targeting the complex biology of GBM, continued research and clinical innovation are imperative to develop more effective and sustainable therapeutic options for patients battling this formidable disease.
胶质母细胞瘤(GBM)仍然是最具侵袭性和致命性的脑癌之一,其特征是快速生长和对传统疗法的耐药性。本综述探讨了 GBM 的靶向治疗的最新进展,强调了血脑屏障(BBB)、血脑肿瘤屏障、肿瘤微环境和遗传突变在影响治疗结果方面的关键作用。详细讨论了 GBM 的主要特征,例如化疗耐药性、缺氧和神经胶质瘤干细胞的存在,对疾病进展和多药耐药性的影响。主要重点是针对这些挑战的创新策略,例如使用单克隆抗体、小分子抑制剂和旨在增强药物穿透 BBB 的新型药物递送系统。此外,还探讨了免疫疗法,特别是免疫检查点抑制剂和基于疫苗的方法,改善患者预后的潜力。综述了最近的临床试验和临床前研究,以提供 GBM 治疗的现状和未来前景的全面概述。还考虑了先进的计算模型和个性化医学方法的整合,旨在针对个体患者的特征量身定制治疗方案,以提高疗效。总的来说,尽管在理解和靶向 GBM 的复杂生物学方面已经取得了重大进展,但为了为对抗这种可怕疾病的患者开发更有效和可持续的治疗选择,仍需要持续的研究和临床创新。