TY - JOUR
T1 - Preclinical therapeutic targets in diffuse midline glioma
AU - Meel, Michaël Hananja
AU - Kaspers, Gertjan J. L.
AU - Hulleman, Esther
PY - 2019/5/1
Y1 - 2019/5/1
N2 - Diffuse midline gliomas (DMG) are rapidly fatal tumors of the midbrain in children, characterized by a diffuse growing pattern and high levels of intrinsic resistance to therapy. The location of these tumors, residing behind the blood-brain barrier (BBB), and the limited knowledge about the biology of these tumors, has hindered the development of effective treatment strategies. However, the introduction of diagnostic biopsies and the implementation of autopsy protocols in several large centers world-wide has allowed for a detailed characterization of these rare tumors. This has resulted in the identification of novel therapeutic targets, as well as major advances in understanding the biology of DMG in relation to therapy resistance. We here provide an overview of the cellular pathways and tumor-specific aberrations that have been targeted in preclinical DMG research, and discuss the advantages and limitations of these therapeutic strategies in relation to therapy resistance and BBB-penetration. Therewith, we aim to provide researchers with a framework for successful preclinical therapy development.
AB - Diffuse midline gliomas (DMG) are rapidly fatal tumors of the midbrain in children, characterized by a diffuse growing pattern and high levels of intrinsic resistance to therapy. The location of these tumors, residing behind the blood-brain barrier (BBB), and the limited knowledge about the biology of these tumors, has hindered the development of effective treatment strategies. However, the introduction of diagnostic biopsies and the implementation of autopsy protocols in several large centers world-wide has allowed for a detailed characterization of these rare tumors. This has resulted in the identification of novel therapeutic targets, as well as major advances in understanding the biology of DMG in relation to therapy resistance. We here provide an overview of the cellular pathways and tumor-specific aberrations that have been targeted in preclinical DMG research, and discuss the advantages and limitations of these therapeutic strategies in relation to therapy resistance and BBB-penetration. Therewith, we aim to provide researchers with a framework for successful preclinical therapy development.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85067018860&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/31202081
U2 - https://doi.org/10.1016/j.drup.2019.06.001
DO - https://doi.org/10.1016/j.drup.2019.06.001
M3 - Article
C2 - 31202081
SN - 1368-7646
VL - 44
SP - 15
EP - 25
JO - Drug resistance updates
JF - Drug resistance updates
ER -