Cerebellar High-Grade Glioma: A Translationally Oriented Review of the Literature.
Cerebellar High-Grade Glioma: A Translationally Oriented Review of the Literature.
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高级别神经胶质癌通常发生在大脑半球，很少出现在大脑的其他地方。从历史上看，发生在小脑的这类肿瘤在临床上的处理方式与其大脑对应部位相同。然而，最近的流行病学研究和分子分析表明，这些肿瘤在可能与治疗干预相关的方式上不同(S)。因此，这篇综述描绘了这一证据的图景，并强调了治疗高级别小脑胶质瘤的新出现的翻译机会。世界卫生组织(WHO)4级小脑胶质瘤是一种罕见的肿瘤，其认知能力落后于幕上脑胶质瘤。与幕上高级别胶质瘤(SHGG)一样，小脑高级别胶质瘤(CHGG)优先影响男性，预后黯淡；然而，它们在年轻人群中更常见。虽然目前对小脑和幕上HGG的治疗是相同的，但最近的分子分析已经确定了可能值得个体化靶向治疗的小脑肿瘤的特征和亚类。最近的一系列CHGG包括：(1)具有毛发状特征的高级别星形细胞瘤(HGAP，约占肿瘤的31%)；(2)H3K27M弥漫性中线胶质瘤(~8%)；(3)异柠檬酸脱氢酶(IDH)野生型胶质母细胞瘤(~43%)。后者具有异常低的表皮生长因子受体(EGFR)频率和高频率的血小板衍生生长因子受体α(PDGFRA)扩增，反映了与幕上IDH野生型肿瘤不同的甲基化类别组成。这些新的分类已经开始揭示小脑HGG的发病机制，并导致针对CHGG适当亚类的个体化治疗。新出现的治疗策略包括靶向丝裂原活化蛋白激酶(MAPK)通路和PDGFRA、溶瘤病毒治疗和免疫治疗。与sHGG相比，小脑的HGG表现出生物学上的差异，对其分子亚类的更好理解有可能促进治疗。
High-grade glial cancers typically arise in the cerebral hemispheres and only rarely elsewhere in the brain. Historically, such tumors arising in the cerebellum have been handled clinically as per their cerebral counterparts. However, recent epidemiological research and molecular analyses have demonstrated that these tumors are different in ways that are likely to be relevant with regard to therapeutic intervention(s). Accordingly, this review charts the landscape of this evidence and highlights emerging translational opportunities for treatments of high-grade cerebellar gliomas. World Health Organization (WHO) grade 4 gliomas of the cerebellum are rare entities whose understanding trails that of their supratentorial counterparts. Like supratentorial high-grade gliomas (sHGG), cerebellar high-grade gliomas (cHGG) preferentially affect males and prognosis is bleak; however, they are more common in a younger population. While current therapy for cerebellar and supratentorial HGG is the same, recent molecular analyses have identified features and subclasses of cerebellar tumors that may merit individualized targeting. One recent series of cHGG included the subclasses of (1) high-grade astrocytoma with piloid features (HGAP, ~31% of tumors); (2) H3K27M diffuse midline glioma (~8%); and (3) isocitrate dehydrogenase (IDH) wildtype glioblastoma (~43%). The latter had an unusually low-frequency of epidermal growth factor receptor (EGFR) and high-frequency of platelet-derived growth factor receptor alpha (PDGFRA) amplification, reflecting a different composition of methylation classes compared to supratentorial IDH-wildtype tumors. These new classifications have begun to reveal insights into the pathogenesis of HGG in the cerebellum and lead toward individualized treatment targeted toward the appropriate subclass of cHGG. Emerging therapeutic strategies include targeting the mitogen-activated protein kinases (MAPK) pathway and PDGFRA, oncolytic virotherapy, and immunotherapy. HGGs of the cerebellum exhibit biological differences compared to sHGG, and improved understanding of their molecular subclasses has the potential to advance treatment.
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影响因子：
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作者：
Filley AC;Henriquez M;Dey M
通讯作者：
Dey M
DOI：
10.1038/s41568-021-00397-3
发表时间：
2021-12
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
Andersen BM;Faust Akl C;Wheeler MA;Chiocca EA;Reardon DA;Quintana FJ
通讯作者：
Quintana FJ
DOI：
10.1097/nen.0000000000000226
发表时间：
2015-09-01
影响因子：
3.2
作者：
Faulkner, Claire;Ellis, Hayley Patricia;Kurian, Kathreena Mary
通讯作者：
Kurian, Kathreena Mary
DOI：
10.1126/science.1257216
发表时间：
2015-01-16
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Flynn RL;Cox KE;Jeitany M;Wakimoto H;Bryll AR;Ganem NJ;Bersani F;Pineda JR;Suvà ML;Benes CH;Haber DA;Boussin FD;Zou L
通讯作者：
Zou L
影响因子：
--
作者：
Li M;Xiao A;Floyd D;Olmez I;Lee J;Godlewski J;Bronisz A;Bhat KPL;Sulman EP;Nakano I;Purow B
通讯作者：
Purow B