Targeting Neuroinflammation in Brain Cancer: Uncovering Mechanisms, Pharmacological Targets, and Neuropharmaceutical Developments.
Targeting Neuroinflammation in Brain Cancer: Uncovering Mechanisms, Pharmacological Targets, and Neuropharmaceutical Developments.
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DOI：
10.3389/fphar.2021.680021
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发表时间：
2021
影响因子：
5.6
通讯作者：
Castro MG
中科院分区：
文献类型：
--
作者：
Alghamri MS;McClellan BL;Hartlage CS;Haase S;Faisal SM;Thalla R;Dabaja A;Banerjee K;Carney SV;Mujeeb AA;Olin MR;Moon JJ;Schwendeman A;Lowenstein PR;Castro MG
胶质瘤是致死率最高的癌症之一，占所有中枢神经系统原发恶性肿瘤的80%。在胶质瘤中，胶质母细胞瘤是最具侵袭性的，患者的中位生存期不到15个 月。最近的分子特征研究揭示了胶质瘤的遗传特征和甲基化状态，并将其与临床预后相关联。与新的胶质瘤分类最相关的分子特征是IDH突变、染色体1p/19q缺失、组蛋白突变和其他遗传参数，如ATRX缺失、TP53和TERT突变，以及DNA甲基化水平。与其他实体肿瘤相似，胶质瘤的进展受到肿瘤微环境中肿瘤细胞和免疫细胞之间复杂相互作用的影响。免疫系统对癌症的反应会影响胶质瘤的生存、增殖和侵袭性。胶质瘤的显著特征包括增强的血管生成，刺激低氧的肿瘤微环境，增加氧化应激，以及免疫抑制环境。这些过程促进了神经炎性肿瘤微环境，从而可能导致血脑屏障(BBB)完整性的丧失。血脑屏障受损的后果是使大脑暴露在来自外周循环的潜在有害浓度的物质中，对神经元信号产生不利影响，并导致异常的免疫细胞渗透；所有这些都可能导致大脑动态平衡的破坏。在这篇综述中，我们首先描述了中枢神经系统肿瘤炎症的独特特征。然后，我们讨论了启动肿瘤的神经炎性微环境的机制及其对肿瘤侵袭和进展的影响。最后，我们还讨论了可用于靶向神经胶质瘤神经炎症的潜在药物干预措施。
Gliomas are one of the most lethal types of cancers accounting for ∼80% of all central nervous system (CNS) primary malignancies. Among gliomas, glioblastomas (GBM) are the most aggressive, characterized by a median patient survival of fewer than 15 months. Recent molecular characterization studies uncovered the genetic signatures and methylation status of gliomas and correlate these with clinical prognosis. The most relevant molecular characteristics for the new glioma classification are IDH mutation, chromosome 1p/19q deletion, histone mutations, and other genetic parameters such as ATRX loss, TP53, and TERT mutations, as well as DNA methylation levels. Similar to other solid tumors, glioma progression is impacted by the complex interactions between the tumor cells and immune cells within the tumor microenvironment. The immune system’s response to cancer can impact the glioma’s survival, proliferation, and invasiveness. Salient characteristics of gliomas include enhanced vascularization, stimulation of a hypoxic tumor microenvironment, increased oxidative stress, and an immune suppressive milieu. These processes promote the neuro-inflammatory tumor microenvironment which can lead to the loss of blood-brain barrier (BBB) integrity. The consequences of a compromised BBB are deleteriously exposing the brain to potentially harmful concentrations of substances from the peripheral circulation, adversely affecting neuronal signaling, and abnormal immune cell infiltration; all of which can lead to disruption of brain homeostasis. In this review, we first describe the unique features of inflammation in CNS tumors. We then discuss the mechanisms of tumor-initiating neuro-inflammatory microenvironment and its impact on tumor invasion and progression. Finally, we also discuss potential pharmacological interventions that can be used to target neuro-inflammation in gliomas.
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影响因子：
8
作者：
Antonios, Joseph P.;Soto, Horacio;Prins, Robert M.
通讯作者：
Prins, Robert M.
影响因子：
15.9
作者：
Bloch, Orin;Crane, Courtney A.;Parsa, Andrew T.
通讯作者：
Parsa, Andrew T.
影响因子：
28.4
作者：
Ahmed N;Brawley V;Hegde M;Bielamowicz K;Kalra M;Landi D;Robertson C;Gray TL;Diouf O;Wakefield A;Ghazi A;Gerken C;Yi Z;Ashoori A;Wu MF;Liu H;Rooney C;Dotti G;Gee A;Su J;Kew Y;Baskin D;Zhang YJ;New P;Grilley B;Stojakovic M;Hicks J;Powell SZ;Brenner MK;Heslop HE;Grossman R;Wels WS;Gottschalk S
通讯作者：
Gottschalk S
影响因子：
4.4
作者：
Akasaki, Y;Liu, G;Yu, JS
通讯作者：
Yu, JS
影响因子：
5.4
作者：
ANEL, A;BUFERNE, M;GOLSTEIN, P
通讯作者：
GOLSTEIN, P