The cellular and developmental biology of medulloblastoma: Current perspectives on experimental therapeutics

Srivastava, Vinit Krishna; Nalbantoglu, Joséphine

doi:10.4161/cbt.9.11.11785

Cited by 11 publications

(7 citation statements)

References 68 publications

(84 reference statements)

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“…Medulloblastomas comprise 4 subtypes: WNT, SHH, group 3, and group 4, which differ regarding histology and clinical outcome (4) and are believed to derive from the deregulation of various signaling pathways in brain development, such as the WNT-pathway and sonic hedgehog (SHH) signaling pathways. Overactivation of these pathways leads to a loss of cell-cycle control and a dysfunctional apoptosis program, allowing for continued growth and tumorigenesis, predominantly in the cerebellum (5).…”

Section: Introductionmentioning

confidence: 99%

EZH2-Regulated DAB2IP Is a Medulloblastoma Tumor Suppressor and a Positive Marker for Survival

Smits

Rijn

Hulleman

et al. 2012

Clinical Cancer Research

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Purpose: Medulloblastoma is the most common malignant brain tumor in children. Despite recent improvements, the molecular mechanisms driving medulloblastoma are not fully understood and further elucidation could provide cues to improve outcome prediction and therapeutic approaches.Experimental Design: Here, we conducted a meta-analysis of mouse and human medulloblastoma gene expression data sets, to identify potential medulloblastoma tumor suppressor genes.Results: We identified DAB2IP, a member of the RAS-GTPase-activating protein family (RAS GAP), and showed that DAB2IP expression is repressed in medulloblastoma by EZH2-induced trimethylation. Moreover, we observed that reduced DAB2IP expression correlates significantly with a poor overall survival of patients with medulloblastoma, independent of metastatic stage. Finally, we showed that ectopic DAB2IP expression enhances stress-induced apoptosis in medulloblastoma cells and that reduced expression of DAB2IP in medulloblastoma cells conveys resistance to irradiation-induced cell death.Conclusion: These results suggest that repression of DAB2IP may at least partly protect medulloblastoma cells from apoptotic cell death. Moreover, DAB2IP may represent a molecular marker to distinguish patients with medulloblastoma at high risk from those with a longer survival prognosis.

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Section: Introductionmentioning

confidence: 99%

EZH2-Regulated DAB2IP Is a Medulloblastoma Tumor Suppressor and a Positive Marker for Survival

Smits

Rijn

Hulleman

et al. 2012

Clinical Cancer Research

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“…MYCN acts downstream of the SHH pathway and its expression has been seen in both nodular and anaplastic MBs. Patients with nodular type of MB have a better survivor rate than those with anaplastic [23]. Desmoplastic/nodular tumors belong to the SHH subgroup.…”

Section: Molecular Subgroups Of Medulloblastomamentioning

confidence: 97%

“…The EGFR receptor is over-expressed in many types of cancer and has also been reported to be expressed in MB [69]. Additional members of the EGFR-family are erythroblastic leukemia viral oncogene homolog 2 (erbB2), erythroblastic leukemia viral oncogene homolog 3 (erbB3), and erythroblastic leukemia viral oncogene homolog 4 (erbB4), which are also expressed in medulloblastoma [23,70]. Medulloblastoma expresses high levels of ErbB-2, whereas in the normal cerebellum the ErbB-2 level is undetectable [68,71].…”

Section: Egfrmentioning

confidence: 99%

Enhanced effects by 4-phenylbutyrate in combination with RTK inhibitors on proliferation in brain tumor cell models

Marino

Sofiadis

Baryawno

et al. 2011

Biochemical and Biophysical Research Communications

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“…Noteworthy, genes that are mainly deregulated in MB, such as WNT , SHH and Notch , as well as the proto-oncogenes RTK (receptor tyrosine kinase) and MYC , are central to molecular pathways controlling cell cycle and growth of CSCs 33–35. Moreover, reports from retrospective studies reveal that several molecular and genetic aberrations that correlate with MB prognosis and outcome36–41 are also involved in the control of CSC stemness,42–47 including neurotrophin-3 receptor ,48 CD15 ,49–51 PTEN ,52 MYC ,53–55 ErbB2 ,56 β-catenin ,57 58 survivin 59 60 and p53 61…”

Section: Mb Classifications and Cscsmentioning

confidence: 99%

Medulloblastoma cancer stem cells: molecular signatures and therapeutic targets

Bahmad

Poppiti

2020

J Clin Pathol

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Medulloblastoma (MB) is the most common malignant primary intracranial neoplasm diagnosed in childhood. Although numerous efforts have been made during the past few years to exploit novel targeted therapies for this aggressive neoplasm, there still exist substantial hitches hindering successful management of MB. Lately, progress in cancer biology has shown evidence that a subpopulation of cells within the tumour, namely cancer stem cells (CSCs), are thought to be responsible for the resistance to most chemotherapeutic agents and radiation therapy, accounting for cancer recurrence. Hence, it is crucial to identify the molecular signatures and genetic aberrations that characterise those CSCs and develop therapies that specifically target them. In this review, we aim to give an overview of the main genetic and molecular cues that depict MB-CSCs and provide a synopsis of the novel therapeutic approaches that specifically target this population of cells to attain enhanced antitumorous effects and therefore overcome resistance to therapy.

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The cellular and developmental biology of medulloblastoma: Current perspectives on experimental therapeutics

Cited by 11 publications

References 68 publications

EZH2-Regulated DAB2IP Is a Medulloblastoma Tumor Suppressor and a Positive Marker for Survival

EZH2-Regulated DAB2IP Is a Medulloblastoma Tumor Suppressor and a Positive Marker for Survival

Enhanced effects by 4-phenylbutyrate in combination with RTK inhibitors on proliferation in brain tumor cell models

Medulloblastoma cancer stem cells: molecular signatures and therapeutic targets

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