Neuroscience Center of Excellence, School of Medicine, Louisiana State University Health New Orleans, New Orleans, LA, USA.
Cancer and Blood Disorders Institute, Johns Hopkins All Children's Hospital, St. Petersburg, FL, USA.
Cancer Metastasis Rev. 2021 Sep;40(3):643-647. doi: 10.1007/s10555-021-09987-x.
Glioblastoma multiforme (GBM) is the most invasive type of glial tumor with poor overall survival, despite advances in surgical resection, chemotherapy, and radiation. One of the main challenges in treating GBM is related to the tumor's location, complex and heterogeneous biology, and high invasiveness. To meet the demand for oxygen and nutrients, growing tumors induce new blood vessels growth. Antibodies directed against vascular endothelial growth factor (VEGF), which promotes angiogenesis, have been developed to limit tumor growth. Bevacizumab (Avastin), an anti-VEGF monoclonal antibody, is the first approved angiogenesis inhibitor with therapeutic promise. However, it has limited efficacy, likely due to adaptive mutations in GBM, leading to overall survival compared to the standard of care in GBM patients. Molecular connections between angiogenesis, inflammation, oxidative stress pathways, and the development of gliomas have been recognized. Improvement in treatment outcomes for patients with GBM requires a multifaceted approach due to the converging dysregulation of signaling pathways. While most GBM clinical trials focus on "anti-angiogenic" modalities, stimulating inflammation resolution is a novel host-centric therapeutic avenue. The selective therapeutic possibilities for targeting the tumor microenvironment, specifically angiogenic and inflammatory pathways expand. So, a combination of agents aiming to interfere with several mechanisms might be beneficial to improve outcomes. Our approach might also be combined with other therapies to enhance sustained effectiveness. Here, we discuss Suramab (anti-angiogenic), LAU-0901 (a platelet-activating factor receptor antagonist), Elovanoid (ELV; a novel lipid mediator), and their combination as potential alternatives to contain GBM growth and invasiveness.
多形性胶质母细胞瘤（GBM）是最具侵袭性的神经胶质瘤，尽管在手术切除、化疗和放疗方面取得了进展，但总体生存率仍较差。治疗 GBM 的主要挑战之一与肿瘤的位置、复杂和异质的生物学以及高侵袭性有关。为了满足肿瘤生长对氧气和营养物质的需求，肿瘤会诱导新的血管生成。针对血管内皮生长因子（VEGF）的抗体已被开发出来，以限制肿瘤生长，VEGF 促进血管生成。贝伐单抗（Avastin）是一种抗 VEGF 的单克隆抗体，是第一种具有治疗潜力的血管生成抑制剂。然而，它的疗效有限，可能是由于 GBM 中的适应性突变，导致 GBM 患者的总生存率与标准治疗相比没有改善。已经认识到血管生成、炎症、氧化应激途径与胶质瘤发生之间的分子联系。由于信号通路的失调趋于一致，需要采用多方面的方法来改善 GBM 患者的治疗效果。虽然大多数 GBM 临床试验都集中在“抗血管生成”模式上，但刺激炎症消退是一种新的以宿主为中心的治疗途径。针对肿瘤微环境，特别是血管生成和炎症途径的选择性治疗可能性正在扩大。因此，针对几种机制的联合治疗可能会有助于改善结果。我们的方法也可能与其他疗法结合使用，以增强持续疗效。在这里，我们讨论了 Suramab（抗血管生成）、LAU-0901（血小板激活因子受体拮抗剂）、Elovanoid（ELV；新型脂质介质）及其组合作为控制 GBM 生长和侵袭性的潜在替代方法。
