Changing paradigms in oncology: Toward noncytotoxic treatments for advanced gliomas
العنوان: | Changing paradigms in oncology: Toward noncytotoxic treatments for advanced gliomas |
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المؤلفون: | Nikolaus von Knebel Doeberitz, Daniel Paech, Dominik Sturm, Stefan Pusch, Sevin Turcan, Yogen Saunthararajah |
المصدر: | International Journal of Cancer. 151:1431-1446 |
بيانات النشر: | Wiley, 2022. |
سنة النشر: | 2022 |
مصطلحات موضوعية: | Cancer Research, Oncology, Brain Neoplasms, Humans, Glioma, Tumor Suppressor Protein p53, Chromatin, Cyclin-Dependent Kinase Inhibitor p16, Transcription Factors |
الوصف: | 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 noncytotoxic glioma-therapy. |
تدمد: | 1097-0215 0020-7136 |
الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d63ca6e93c66a15d6b425790a3b470c7Test https://doi.org/10.1002/ijc.34131Test |
حقوق: | OPEN |
رقم الانضمام: | edsair.doi.dedup.....d63ca6e93c66a15d6b425790a3b470c7 |
قاعدة البيانات: | OpenAIRE |
تدمد: | 10970215 00207136 |
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