Targeting MYCN in Molecularly Defined Malignant Brain Tumors

被引：23

作者：

Borgenvik, Anna ^{[1
]}

Cancer, Matko ^{[2
]}

Hutter, Sonja ^{[1
]}

Swartling, Fredrik J. ^{[1
]}

机构：

[1] Uppsala Univ, Dept Immunol Genet & Pathol, Sci Life Lab, Rudbeck Lab, Uppsala, Sweden

[2] Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden

来源：

FRONTIERS IN ONCOLOGY | 2021年 / 10卷

基金：

欧洲研究理事会; 瑞典研究理事会;

关键词：

MYCN; brain tumor; targeted therapies; c-MYC; OCT4; medulloblastoma; glioma; N-MYC; C-MYC; AURORA KINASE; INHIBITION; GLIOBLASTOMA; GLIOMAS; PHOSPHORYLATION; DIFFERENTIATION; STABILIZATION; ACTIVATION;

D O I：

10.3389/fonc.2020.626751

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Misregulation of MYC genes, causing MYC overexpression or protein stabilization, is frequently found in malignant brain tumors highlighting their important roles as oncogenes. Brain tumors in children are the most lethal of all pediatric malignancies and the most common malignant primary adult brain tumor, glioblastoma, is still practically incurable. MYCN is one of three MYC family members and is crucial for normal brain development. It is associated with poor prognosis in many malignant pediatric brain tumor types and is focally amplified in specific adult brain tumors. Targeting MYCN has proved to be challenging due to its undruggable nature as a transcription factor and for its importance in regulating developmental programs also in healthy cells. In this review, we will discuss efforts made to circumvent the difficulty of targeting MYCN specifically by using direct or indirect measures to treat MYCN-driven brain tumors. We will further consider the mechanism of action of these measures and suggest which molecularly defined brain tumor patients that might benefit from MYCN-directed precision therapies.

引用

页数：14

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