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The Capital Region of Denmark - a part of Copenhagen University Hospital
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Targeting glioma stem-like cell survival and chemoresistance through inhibition of lysine-specific histone demethylase KDM2B

Research output: Contribution to journalJournal articleResearchpeer-review

DOI

  1. Angiotensinogen promoter methylation predicts bevacizumab treatment response of patients with recurrent glioblastoma

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Using microarray-based subtyping methods for breast cancer in the era of high-throughput RNA sequencing

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Molecular subtype classification of urothelial carcinoma in Lynch syndrome

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Characterization of genetic intratumor heterogeneity in colorectal cancer and matching patient-derived spheroid cultures

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. Angiotensinogen promoter methylation predicts bevacizumab treatment response of patients with recurrent glioblastoma

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Systemic Immune Modulation in Gliomas: Prognostic Value of Plasma IL-6, YKL-40, and Genetic Variation in YKL-40

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. ABCB1 single-nucleotide variants and survival in patients with glioblastoma treated with radiotherapy concomitant with temozolomide

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  4. Early Postoperative 18F-FET PET/MRI for Pediatric Brain and Spinal Cord Tumors

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Glioblastoma (GBM) ranks among the most lethal cancers, with current therapies offering only palliation. Inter- and intrapatient heterogeneity is a hallmark of GBM, with epigenetically distinct cancer stem-like cells (CSCs) at the apex. Targeting GSCs remains a challenging task because of their unique biology, resemblance to normal neural stem/progenitor cells, and resistance to standard cytotoxic therapy. Here, we find that the chromatin regulator, JmjC domain histone H3K36me2/me1 demethylase KDM2B, is highly expressed in glioblastoma surgical specimens compared to normal brain. Targeting KDM2B function genetically or pharmacologically impaired the survival of patient-derived primary glioblastoma cells through the induction of DNA damage and apoptosis, sensitizing them to chemotherapy. KDM2B loss decreased the GSC pool, which was potentiated by coadministration of chemotherapy. Collectively, our results demonstrate KDM2B is crucial for glioblastoma maintenance, with inhibition causing loss of GSC survival, genomic stability, and chemoresistance.

Original languageEnglish
JournalMolecular Oncology
Volume12
Issue number3
Pages (from-to)406-420
Number of pages15
ISSN1574-7891
DOIs
Publication statusPublished - Mar 2018

ID: 55716453