Targeting MYCN in Molecularly Defined Malignant Brain Tumors

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...

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Published inFrontiers in oncology Vol. 10; p. 626751
Main Authors Borgenvik, Anna, Čančer, Matko, Hutter, Sonja, Swartling, Fredrik J.
Format Journal Article
LanguageEnglish
Published Switzerland Frontiers Media S.A 28.01.2021
Subjects
brain tumor
c-MYC
glioma
medulloblastoma
MYCN
OCT4
Oncology
targeted therapies
OCT4
MYCN
targeted therapies
c-MYC
medulloblastoma
brain tumor
glioma
Online AccessGet full text
ISSN2234-943X
2234-943X
DOI10.3389/fonc.2020.626751

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Abstract 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.
AbstractList 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.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.
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.
Author Hutter, Sonja
Borgenvik, Anna
Swartling, Fredrik J.
Čančer, Matko
AuthorAffiliation 2 Department of Oncology-Pathology, Karolinska Institutet , Stockholm , Sweden
1 Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Rudbeck Laboratory, Uppsala University , Uppsala , Sweden
AuthorAffiliation_xml – name: 2 Department of Oncology-Pathology, Karolinska Institutet , Stockholm , Sweden
– name: 1 Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Rudbeck Laboratory, Uppsala University , Uppsala , Sweden
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  givenname: Fredrik J.
  surname: Swartling
  fullname: Swartling, Fredrik J.
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Keywords OCT4
MYCN
targeted therapies
c-MYC
medulloblastoma
brain tumor
glioma
Language English
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Edited by: Yusuke Suenaga, Chiba Cancer Center, Japan
This article was submitted to Molecular and Cellular Oncology, a section of the journal Frontiers in Oncology
Reviewed by: Eishu Hirata, Kanazawa University, Japan; Sabina Quader, Innovation Centre of NanoMedicine (iCONM), Japan
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Snippet Misregulation of MYC genes, causing MYC overexpression or protein stabilization, is frequently found in malignant brain tumors highlighting their important...
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SubjectTerms brain tumor
c-MYC
glioma
medulloblastoma
MYCN
OCT4
Oncology
targeted therapies
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Title Targeting MYCN in Molecularly Defined Malignant Brain Tumors
URI https://www.ncbi.nlm.nih.gov/pubmed/33585252
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