Journal Article (Review Article)

DKFZ-2022-01045

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Changing paradigms in oncology: toward non-cytotoxic treatments for advanced gliomas.

von Knebel Doeberitz, N. (First author)DKFZ* ; Paech, D.DKFZ* ; Sturm, D.DKFZ* ; Pusch, S.DKFZ* ; Turcan, S. ; Saunthararajah, Y.

2022
Wiley-Liss Bognor Regis

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Please use a persistent id in citations: doi:10.1002/ijc.34131

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.

Keyword(s): Cancer Epigenetics ; Epigenetic Glioma Therapy ; Glioma ; Glioma Therapy ; Neurooncology

Note: #EA:E010# / 2022 Nov 1;151(9):1431-1446

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Contributing Institute(s):

1. E010 Radiologie (E010)
2. Pediatric Glioma (B360)
3. DKTK HD zentral (HD01)
4. KKE Neuropathologie (B300)
5. B062 Pädiatrische Neuroonkologie (B062)

Research Program(s):

1. 315 - Bildgebung und Radioonkologie (POF4-315) (POF4-315)

Appears in the scientific report 2022

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DEAL Wiley ; Essential Science Indicators ; IF >= 5 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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