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@ARTICLE{Rechberger:285048,
author = {J. S. Rechberger and S. M. Bouchal and E. A. Power and L.
Nonnenbroich$^*$ and C. L. Nesvick and D. J. Daniels},
title = {{B}ench-to-bedside investigations of {H}3 {K}27-altered
diffuse midline glioma: drug targets and potential
pharmacotherapies.},
journal = {Expert opinion on therapeutic targets},
volume = {27},
number = {11},
issn = {1460-0412},
address = {Abingdon, Oxon},
publisher = {Routledge, Taylor $\&$ Francis},
reportid = {DKFZ-2023-02191},
pages = {1071-1086},
year = {2023},
note = {2023 Jul-Dec;27(11):1071-1086},
abstract = {H3 K27-altered diffuse midline glioma (DMG) is the most
common malignant brainstem tumor in the pediatric
population. Despite enormous preclinical and clinical
efforts, the prognosis remains dismal, with fewer than
$10\%$ of patients surviving for two years after diagnosis.
Fractionated radiation remains the only standard treatment
options for DMG. Developing novel treatments and therapeutic
delivery methods is critical to improving outcomes in this
devastating disease.This review addresses recent advances in
molecularly targeted pharmacotherapy and immunotherapy in
DMG. The clinical presentation, diagnostic workup, unique
pathological challenges, and current clinical trials are
highlighted throughout.Promising pharmacotherapies targeting
various components of DMG pathology and the application of
immunotherapies have the potential to improve patient
outcomes. However, novel approaches are needed to truly
revolutionize treatment for this tumor. First, combinational
therapy should be employed, as DMG can develop resistance to
single-agent approaches and many therapies are susceptible
to rapid clearance from the brain. Second, drug-tumor
residence time, i.e. the time for which a therapeutic is
present at efficacious concentrations within the tumor, must
be maximized to facilitate a durable treatment response.
Engineering extended drug delivery methods with minimal
off-tumor toxicity should be a focus of future studies.},
subtyp = {Review Article},
keywords = {Diffuse midline glioma (Other) / H3 K27-altered (Other) /
H3 K27M (Other) / ONC201 (Other) / blood-brain barrier
(Other) / convection-enhanced delivery (Other) / diffuse
intrinsic pontine glioma (Other) / histone (Other) /
immunotherapy (Other) / targeted therapy (Other)},
cin = {B310 / HD01},
ddc = {610},
cid = {I:(DE-He78)B310-20160331 / I:(DE-He78)HD01-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:37897190},
doi = {10.1080/14728222.2023.2277232},
url = {https://inrepo02.dkfz.de/record/285048},
}