The Landscape of Novel Therapeutics and Challenges in Glioblastoma Multiforme: Contemporary State and Future Directions.
The Landscape of Novel Therapeutics and Challenges in Glioblastoma Multiforme: Contemporary State and Future Directions.
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DOI：
10.3390/ph13110389
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发表时间：
2020-11-14
期刊：
影响因子：
--
通讯作者：
Ansstas G
中科院分区：
文献类型：
--
作者：
Khaddour K;Johanns TM;Ansstas G
背景资料：多形性胶质母细胞瘤是一种恶性颅内肿瘤，由于缺乏有效的批准药物和肿瘤的侵袭性，其发病率和死亡率较高，因此构成了治疗挑战。然而，最近有广泛的研究来解决肿瘤对药物化合物的耐药性的原因，这导致了几项研究有希望的治疗方法的临床试验。方法：我们回顾了自2010年以来PUBMED发表的文献和截至2020年9月15日的几篇年会摘要。选定的文章包括与胶质母细胞瘤肿瘤生物学、原创基础研究、临床试验、开创性评论和荟萃分析主题相关的文章。我们根据收集到的关于治疗过程中遇到的挑战性因素的证据进行了讨论，并强调了包括免疫疗法和靶向药物在内的新型疗法的相关试验。结果如下：选定的文献揭示了与研究性治疗的低疗效相关的四个主要因素，包括：（1）血脑屏障;（2）免疫抑制微环境;（3）遗传异质性;（4）与既往全身治疗相关的外部因素，可调节肿瘤微环境。本综述中讨论的研究性治疗分为免疫治疗和靶向治疗。免疫治疗包括：（1）免疫检查点抑制剂;（2）过继性细胞转移治疗;（3）治疗性疫苗;（4）溶瘤病毒治疗。靶向治疗包括酪氨酸激酶抑制剂和其他受体抑制剂。最后，我们提供了我们对胶质母细胞瘤治疗的未来方向的看法。结论：尽管在胶质母细胞瘤的有效治疗方法的开发方面取得了有限的成功，但许多治疗方法具有潜在的希望，包括免疫疗法和新型组合药物。解决胶质母细胞瘤的分子景观和耐药性免疫抑制性质对于进一步开发有效治疗至关重要。
Background: Glioblastoma multiforme is a malignant intracranial neoplasm that constitutes a therapeutic challenge because of the associated high morbidity and mortality given the lack of effective approved medication and aggressive nature of the tumor. However, there has been extensive research recently to address the reasons implicated in the resistant nature of the tumor to pharmaceutical compounds, which have resulted in several clinical trials investigating promising treatment approaches. Methods: We reviewed literature published since 2010 from PUBMED and several annual meeting abstracts through 15 September 2020. Selected articles included those relevant to topics of glioblastoma tumor biology, original basic research, clinical trials, seminal reviews, and meta-analyses. We provide a discussion based on the collected evidence regarding the challenging factors encountered during treatment, and we highlighted the relevant trials of novel therapies including immunotherapy and targeted medication. Results: Selected literature revealed four main factors implicated in the low efficacy encountered with investigational treatments which included: (1) blood-brain barrier; (2) immunosuppressive microenvironment; (3) genetic heterogeneity; (4) external factors related to previous systemic treatment that can modulate tumor microenvironment. Investigational therapies discussed in this review were classified as immunotherapy and targeted therapy. Immunotherapy included: (1) immune checkpoint inhibitors; (2) adoptive cell transfer therapy; (3) therapeutic vaccines; (4) oncolytic virus therapy. Targeted therapy included tyrosine kinase inhibitors and other receptor inhibitors. Finally, we provide our perspective on future directions in treatment of glioblastoma. Conclusion: Despite the limited success in development of effective therapeutics in glioblastoma, many treatment approaches hold potential promise including immunotherapy and novel combinational drugs. Addressing the molecular landscape and resistant immunosuppressive nature of glioblastoma are imperative in further development of effective treatments.
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