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Udgivet

Targeting glioma stem-like cell survival and chemoresistance through inhibition of lysine-specific histone demethylase KDM2B

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

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

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Molecular subtype classification of urothelial carcinoma in Lynch syndrome

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Vis graf over relationer

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.

OriginalsprogEngelsk
TidsskriftMolecular Oncology
Vol/bind12
Udgave nummer3
Sider (fra-til)406-420
Antal sider15
ISSN1574-7891
DOI
StatusUdgivet - mar. 2018

ID: 55716453