Modulation of Ciliogenesis in Glioma Stem Cells

Study Overview
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Brief Summary
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The study aims at investigating the cilium-related transcriptome in patients-derived glioblastoma stem cells and the potential impact of modulation of cilium players in vitro, in vivo and ex vivo in glioblastoma brain organoids. Moreover, drugs inhibiting cilia disassembly will be tested. Finally, the potential prognostic role of a cilium-related gene expression signature in glioblastoma will be assessed.

Official Title
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Control of Growth and Invasiveness of Glioblastoma by Modulation of Ciliogenesis in Glioma Stem Cells. A Novel Target Against Glioblastoma for Precision Medicine. RF-2019-12368786

Conditions
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Glioblastoma, Glioma, Malignant

Intervention / Treatment
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* Other: Biological sample collection
* Other: Dissecting ciliogenesis players
* Diagnostic Test: Validating ciliogenesis players


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: To be enrolled in the study patients must: Have a radiological diagnosis of supratentorial glioblastoma, or Have a radiological diagnosis of first recurrence of a primary supratentorial glioblastoma (for which a formal histopathologic diagnosis of glioblastoma had been made at first surgery), according with RANO criteria (Wen, 2010); Be a candidate to neurosurgery for glioblastoma at the Operational Unit of Neurosurgery FPG; Be of an age of 18 years or above; Provide written informed consent for participation to the study. Exclusion criteria To be enrolled in the study patients must not: Have not enough pathological material removed at surgery available both for mandatory routine histopathological diagnosis and for the present study, as judged by the Principal Investigator; Have not a definitive pathological diagnosis of a primary supratentorial GBM, according with 2016 WHO classification.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Biological sample collection<br>Collection of tumor tissue and PBMC for the generation of glioblastoma stem cell cultures and brain organoids. | Other: Biological sample collection<br>* Collection of tumor tissue and blood for stem cell culture and organoids generation.<br>Other: Dissecting ciliogenesis players<br>* Assessment of cilium-related transcriptome in glioblastoma stem cells. Modulation of cilium-related genes and administration of cilium-targeted drugs to glioblastoma stem cells in vitro and ex vivo in glioblastoma brain organoids.<br>Diagnostic Test: Validating ciliogenesis players<br>* Cilium-related signature will be studied in tumor tissue to evaluate its prognostic role.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biological | Correlation between modulation of cilia disassembly complex genes, and tumor growth and invasion in brain organoids. | Through study completion, an average of 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cilia disassembly complex, Nek2, glioblastoma stem cells