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@ARTICLE{vonKnebelDoeberitz:180028,
author = {N. von Knebel Doeberitz$^*$ and D. Paech$^*$ and D.
Sturm$^*$ and S. Pusch$^*$ and S. Turcan and Y.
Saunthararajah},
title = {{C}hanging paradigms in oncology: toward non-cytotoxic
treatments for advanced gliomas.},
journal = {International journal of cancer},
volume = {151},
number = {9},
issn = {0020-7136},
address = {Bognor Regis},
publisher = {Wiley-Liss},
reportid = {DKFZ-2022-01045},
pages = {1431-1446},
year = {2022},
note = {#EA:E010# / 2022 Nov 1;151(9):1431-1446},
abstract = {Glial-lineage malignancies (gliomas) recurrently mutate
and/or delete the master regulators of apoptosis p53 and/or
p16/CDKN2A, undermining apoptosis-intending (cytotoxic)
treatments. By contrast to disrupted p53/p16, glioma cells
are live-wired with the master transcription factor circuits
that specify and drive glial lineage-fates: these
transcription factors activate early-glial and replication
programs as expected, but fail in their other usual function
of forcing onward glial lineage-maturation - late-glial
genes have constitutively 'closed' chromatin requiring
chromatin-remodeling for activation - glioma-genesis
disrupts several epigenetic components needed to perform
this work, and simultaneously amplifies repressing
epigenetic machinery instead. Pharmacologic inhibition of
repressing epigenetic enzymes thus allows activation of
late-glial genes and terminates glioma self-replication
(self-replication = replication without lineage-maturation),
independent of p53/p16/apoptosis. Lineage-specifying master
transcription factors therefore contrast with p53/p16 in
being enriched in self-replicating glioma cells, reveal a
cause-effect relationship between aberrant epigenetic
repression of late-lineage programs and malignant
self-replication, and point to specific epigenetic targets
for non-cytotoxic glioma-therapy.},
subtyp = {Review Article},
keywords = {Cancer Epigenetics (Other) / Epigenetic Glioma Therapy
(Other) / Glioma (Other) / Glioma Therapy (Other) /
Neurooncology (Other)},
cin = {E010 / B360 / HD01 / B300 / B062},
ddc = {610},
cid = {I:(DE-He78)E010-20160331 / I:(DE-He78)B360-20160331 /
I:(DE-He78)HD01-20160331 / I:(DE-He78)B300-20160331 /
I:(DE-He78)B062-20160331},
pnm = {315 - Bildgebung und Radioonkologie (POF4-315)},
pid = {G:(DE-HGF)POF4-315},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:35603902},
doi = {10.1002/ijc.34131},
url = {https://inrepo02.dkfz.de/record/180028},
}