Brain glioblastoma

Summary

Brain glioblastoma (MONDO:0002501) is a disease with 3 cohort genes and 39 clinical trials. Molecularly, BCR::NTRK2 Fusion confers sensitivity to Entrectinib in Brain Glioblastoma Multiforme (CIViC Level C). Top therapeutic interventions include temozolomide, avelumab, and belinostat.

At a glance

• Cohort genes: 3
• Clinical trials: 39
• Precision-medicine evidence (CIViC): 1 subtype–drug association

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	brain glioblastoma
Mondo ID	MONDO:0002501
EFO	EFO:0006545
DOID	DOID:3073
NCIT	C4642
SNOMED CT	276828006
UMLS	C0349543
MedGen	138100
GARD	0023150
Anatomy (UBERON)	UBERON:0000955
Is cancer (heuristic)	no

Also known as: brain glioblastoma · brain glioblastoma (disease) · brain glioblastoma multiforme · brain glioblastoma multiforme (disease) · glioblastoma multiforme of brain · glioblastoma multiforme of the brain · grade IV astrocytic tumour of brain · grade IV brain astrocytic tumour

Disease family

An umbrella term covering 3 Mondo subtypes.

Classification path: human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › cancer › nervous system cancer › central nervous system cancer › brain cancer › brain glioma › brain glioblastoma

Related subtypes (7): brain oligodendroglioma, brain stem glioma, diencephalic astrocytomas, childhood cerebral astrocytoma, ependymal tumor of brain, gliomatosis cerebri, chordoid glioma of the third ventricle

Subtypes (3): gliosarcoma, giant cell glioblastoma, brain stem glioblastoma

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
EGFR	Orphanet:251576	Gliosarcoma
EGFR	Orphanet:251579	Giant cell glioblastoma

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
civic_only	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
EGFR	HGNC:3236	ENSG00000146648	P00533	Epidermal growth factor receptor	civic_evidence
H3-3A	HGNC:4764	ENSG00000163041	P84243	Histone H3.3	civic_evidence
H3C2	HGNC:4776	ENSG00000286522	P68431	Histone H3.1	civic_evidence

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
EGFR	Epidermal growth factor receptor	Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses.
H3-3A	Histone H3.3	Variant histone H3 which replaces conventional H3 in a wide range of nucleosomes in active genes.
H3C2	Histone H3.1	Core component of nucleosome.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.33

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Kinase	1	9.2×	0.209
Other/Unknown	2	1.2×	0.587

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
EGFR	Kinase	yes	2.7.10.1	Rcpt_L-dom, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom
H3-3A	Other/Unknown	no		Histone_H3/CENP-A, H2A/H2B/H3, Histone-fold
H3C2	Other/Unknown	no		Histone_H3/CENP-A, H2A/H2B/H3, Histone-fold

Expression context

Cohort genes with no expression data: 0.

3 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
gingiva	1
gingival epithelium	1
nipple	1
ganglionic eminence	1
monocyte	1
ventricular zone	1
adrenal tissue	1
bone marrow cell	1
colonic epithelium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
EGFR	285	ubiquitous	marker	nipple, gingiva, gingival epithelium
H3-3A	134	ubiquitous	marker	ganglionic eminence, monocyte, ventricular zone
H3C2	94	ubiquitous	marker	adrenal tissue, colonic epithelium, bone marrow cell

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
EGFR	18,421
H3C2	3,550
H3-3A	1,595

Structural data

PDB: 3 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
H3C2	P68431	548
EGFR	P00533	388
H3-3A	P84243	103

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 86. Enrichment computed across 3 evidence-associated genes (3 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
RNA Polymerase I Promoter Opening	2	122.8×	7e-04	H3-3A, H3C2
DNA methylation	2	119.0×	7e-04	H3-3A, H3C2
FXIIa activates plasma kallikrein-kinin system	2	115.3×	7e-04	H3-3A, H3C2
SIRT1 negatively regulates rRNA expression	2	113.6×	7e-04	H3-3A, H3C2
Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3	2	112.0×	7e-04	H3-3A, H3C2
Assembly of the ORC complex at the origin of replication	2	110.3×	7e-04	H3-3A, H3C2
Chromatin modifications during the maternal to zygotic transition (MZT)	2	108.8×	7e-04	H3-3A, H3C2
Regulation of endogenous retroelements by the Human Silencing Hub (HUSH) complex	2	108.8×	7e-04	H3-3A, H3C2
Condensation of Prophase Chromosomes	2	104.3×	7e-04	H3-3A, H3C2
Defective pyroptosis	2	104.3×	7e-04	H3-3A, H3C2
PRC2 methylates histones and DNA	2	101.5×	7e-04	H3-3A, H3C2
ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression	2	101.5×	7e-04	H3-3A, H3C2
CHD6, CHD7, CHD8, CHD9 subfamily	2	98.9×	7e-04	H3-3A, H3C2
Transcriptional regulation by small RNAs	2	96.4×	7e-04	H3-3A, H3C2
NuRD complex assembly	2	94.0×	7e-04	H3-3A, H3C2
Meiotic recombination	2	86.5×	7e-04	H3-3A, H3C2
Interaction of NuRD complexes with transcription factors	2	84.6×	7e-04	H3-3A, H3C2
Transcriptional regulation of granulopoiesis	2	83.7×	7e-04	H3-3A, H3C2
Pre-NOTCH Transcription and Translation	2	81.9×	7e-04	H3-3A, H3C2
B-WICH complex positively regulates rRNA expression	2	81.0×	7e-04	H3-3A, H3C2
RNA Polymerase I Promoter Escape	2	81.0×	7e-04	H3-3A, H3C2
Formation of the beta-catenin:TCF transactivating complex	2	80.1×	7e-04	H3-3A, H3C2
RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function	2	80.1×	7e-04	H3-3A, H3C2
Negative Regulation of CDH1 Gene Transcription	2	80.1×	7e-04	H3-3A, H3C2
Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs)	2	78.5×	7e-04	H3-3A, H3C2
Regulation of PD-L1(CD274) transcription	2	72.5×	8e-04	H3-3A, H3C2
CHD1 and CHD2 subfamily	2	72.5×	8e-04	H3-3A, H3C2
Regulation of endogenous retroelements by KRAB-ZFP proteins	2	71.2×	8e-04	H3-3A, H3C2
NoRC negatively regulates rRNA expression	2	69.8×	8e-04	H3-3A, H3C2
Amyloid fiber formation	2	68.6×	8e-04	H3-3A, H3C2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
telomere organization	2	416.1×	5e-04	H3-3A, H3C2
positive regulation of cell growth	2	122.1×	0.003	EGFR, H3-3A
negative regulation of cardiocyte differentiation	1	5617.3×	0.003	EGFR
nucleosome assembly	2	93.6×	0.003	H3-3A, H3C2
positive regulation of protein kinase C signaling	1	1872.4×	0.006	EGFR
morphogenesis of an epithelial fold	1	1404.3×	0.006	EGFR
response to UV-A	1	1404.3×	0.006	EGFR
negative regulation of chromosome condensation	1	1404.3×	0.006	H3-3A
pericentric heterochromatin formation	1	1123.5×	0.006	H3-3A
regulation of peptidyl-tyrosine phosphorylation	1	1123.5×	0.006	EGFR
salivary gland morphogenesis	1	802.5×	0.008	EGFR
protein insertion into membrane	1	702.2×	0.008	EGFR
ubiquitin-dependent endocytosis	1	624.1×	0.009	EGFR
ERBB2-EGFR signaling pathway	1	561.7×	0.009	EGFR
cerebral cortex cell migration	1	510.7×	0.009	EGFR
subtelomeric heterochromatin formation	1	510.7×	0.009	H3-3A
eyelid development in camera-type eye	1	351.1×	0.011	EGFR
digestive tract morphogenesis	1	330.4×	0.011	EGFR
positive regulation of phosphorylation	1	280.9×	0.011	EGFR
muscle cell differentiation	1	280.9×	0.011	H3-3A
xenobiotic transport	1	280.9×	0.011	EGFR
embryonic placenta development	1	255.3×	0.011	EGFR
positive regulation of peptidyl-serine phosphorylation	1	255.3×	0.011	EGFR
negative regulation of epidermal growth factor receptor signaling pathway	1	255.3×	0.011	EGFR
oocyte maturation	1	200.6×	0.014	H3-3A
positive regulation of DNA replication	1	193.7×	0.014	EGFR
nucleus organization	1	187.2×	0.014	H3-3A
positive regulation of epidermal growth factor receptor signaling pathway	1	165.2×	0.015	EGFR
cellular response to estradiol stimulus	1	137.0×	0.017	EGFR
positive regulation of G1/S transition of mitotic cell cycle	1	133.8×	0.017	EGFR

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 2

Druggability breadth: 2 of 3 evidence-associated genes (67%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
EGFR	LEVODOPA

Top cohort targets by molecule count

Symbol	Molecules	Max phase
EGFR	175	4
H3-3A	0	0
H3C2	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
LEVODOPA	4	EGFR
CLOTRIMAZOLE	4	EGFR
ERLOTINIB HYDROCHLORIDE	4	EGFR
CISPLATIN	4	EGFR
PONATINIB	4	EGFR
AFATINIB	4	EGFR
CHROMIC CHLORIDE	4	EGFR
BACITRACIN	4	EGFR
ZINC CHLORIDE	4	EGFR
LAPATINIB DITOSYLATE	4	EGFR
VEMURAFENIB	4	EGFR
FEDRATINIB	4	EGFR
AXITINIB	4	EGFR
SORAFENIB	4	EGFR
DASATINIB ANHYDROUS	4	EGFR
NICLOSAMIDE	4	EGFR
SELUMETINIB	4	EGFR
TERFENADINE	4	EGFR
ALECTINIB	4	EGFR
NERATINIB	4	EGFR
IBRUTINIB	4	EGFR
AFATINIB DIMALEATE	4	EGFR
CABOZANTINIB	4	EGFR
DACOMITINIB	4	EGFR
DACOMITINIB ANHYDROUS	4	EGFR
CERITINIB	4	EGFR
VANDETANIB	4	EGFR
TRIBROMSALAN	4	EGFR
BOSUTINIB	4	EGFR
BITHIONOL	4	EGFR

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
EGFR	6,531	Binding:6211, Functional:173, ADMET:138, Toxicity:9
H3-3A	6	Binding:6

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
EGFR	2.7.10.1	receptor protein-tyrosine kinase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
EGFR	6,531

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

30 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
LEVODOPA	4	EGFR
CLOTRIMAZOLE	4	EGFR
ERLOTINIB HYDROCHLORIDE	4	EGFR
CISPLATIN	4	EGFR
PONATINIB	4	EGFR
AFATINIB	4	EGFR
CHROMIC CHLORIDE	4	EGFR
BACITRACIN	4	EGFR
ZINC CHLORIDE	4	EGFR
LAPATINIB DITOSYLATE	4	EGFR
VEMURAFENIB	4	EGFR
FEDRATINIB	4	EGFR
AXITINIB	4	EGFR
SORAFENIB	4	EGFR
DASATINIB ANHYDROUS	4	EGFR
NICLOSAMIDE	4	EGFR
SELUMETINIB	4	EGFR
TERFENADINE	4	EGFR
ALECTINIB	4	EGFR
NERATINIB	4	EGFR
IBRUTINIB	4	EGFR
AFATINIB DIMALEATE	4	EGFR
CABOZANTINIB	4	EGFR
DACOMITINIB	4	EGFR
DACOMITINIB ANHYDROUS	4	EGFR
CERITINIB	4	EGFR
VANDETANIB	4	EGFR
TRIBROMSALAN	4	EGFR
BOSUTINIB	4	EGFR
BITHIONOL	4	EGFR

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	EGFR
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	H3-3A, H3C2

Undrugged target profiles

2 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
H3-3A	6	—
H3C2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 39.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE1	12
Not specified	9
PHASE2	8
EARLY_PHASE1	5
PHASE1/PHASE2	3
PHASE3	1
PHASE2/PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05685004	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	Study of Neoantigen-specific Adoptive T Cell Therapy for Newly Diagnosed MGMT Negative Glioblastoma Multiforme (GBM)
NCT03633552	PHASE3	UNKNOWN	Efficacy of Two Temozolomide Regimens in Adjuvant Treatment of Patients With Brain High Grade Glioma
NCT02649582	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Adjuvant Dendritic Cell-immunotherapy Plus Temozolomide in Glioblastoma Patients
NCT06991101	PHASE2	RECRUITING	Ruxolitinib With Radiation and Temozolomide Compared to Radiation and Temozolomide for Newly Diagnosed Glioblastoma
NCT00003456	PHASE2	COMPLETED	Antineoplaston Therapy in Treating Patients With Newly-diagnosed Glioblastoma Multiforme
NCT00003474	PHASE2	COMPLETED	Antineoplaston Therapy in Treating Adults With Residual/Recurrent/Progressive Glioblastoma Multiforme
NCT02137759	PHASE2	UNKNOWN	MRSI to Predict Response to RT/TMZ ± Belinostat in GBM
NCT02302235	PHASE2	COMPLETED	Ketogenic Diet Treatment Adjunctive to Radiation and Chemotherapy in Glioblastoma Multiforme: a Pilot Study
NCT02474966	PHASE2	COMPLETED	Effect of Deep TMS on the Permeability of the BBB in Patients With Glioblastoma Multiforme: a Pilot Study
NCT03047473	PHASE2	COMPLETED	Avelumab in Patients With Newly Diagnosed Glioblastoma Multiforme
NCT03665545	PHASE1/PHASE2	COMPLETED	Pembrolizumab in Association With the IMA950/Poly-ICLC for Relapsing Glioblastoma
NCT04388475	PHASE2	COMPLETED	Open-label Study Investigating of OKN-007 Combined With Temozolomide in Patients With Recurrent Glioblastoma
NCT06186440	PHASE1/PHASE2	UNKNOWN	Cisplatin Plus Temozolomide Compared With Temozolomide in Patients With MGMT Promotor Unmethylated Glioblastoma
NCT03170141	PHASE1	ENROLLING_BY_INVITATION	Immunogene-modified T (IgT) Cells Against Glioblastoma Multiforme
NCT03657576	PHASE1	ACTIVE_NOT_RECRUITING	Trial of C134 in Patients With Recurrent GBM
NCT05363826	PHASE1	RECRUITING	Intracavitary Photodynamic Therapy as an Adjuvant to Resection of Glioblastoma or Gliosarcoma Using IV Photobac®
NCT05627323	PHASE1	ACTIVE_NOT_RECRUITING	CAR T Cells in Patients With MMP2+ Recurrent or Progressive Glioblastoma
NCT06815432	PHASE1	RECRUITING	GPC-3 CAR T CELLS FOR Recurrent GPC-3 Positive Glioblastoma
NCT07179328	PHASE1	RECRUITING	Focused Ultrasound Blood-Brain Barrier Disruption for the Treatment of High-Grade Glioma in Patients Undergoing Standard Chemotherapy
NCT07464925	PHASE1	RECRUITING	A Phase 1 Safety and Dose Finding Study of GLIX1 in Adults With Recurrent or Progressive High-grade Glioma
NCT04222309	PHASE1	SUSPENDED	Laparoscopically Harvested Omental Free Tissue Autograft to Bypass the Blood Brain Barrier (BBB) in Human Recurrent Glioblastoma Multiforme (rGBM)
NCT04842513	PHASE1	COMPLETED	Multi Peptide Vaccination with XS15 in Addition to Standard Postoperative Radiation Therapy and Temozolomide Chemotherapy in Newly Diagnosed Glioblastoma
NCT04968366	PHASE1	COMPLETED	Safety & Efficacy of DC Vaccine and TMZ for the Treatment of Newly-diagnosed Glioblastoma After Surgery
NCT05095441	PHASE1	UNKNOWN	A Clinical Study of Intratumoral MVR-C5252 (C5252) in Patients With Recurrent or Progressive Glioblastoma
NCT06193174	PHASE1	TERMINATED	Re-Administration of C134 in Patients With Recurrent GBM (C134-HSV-1)
NCT05076513	EARLY_PHASE1	ACTIVE_NOT_RECRUITING	Trial of Niraparib in Participants With Newly-diagnosed Glioblastoma and Recurrent Glioma
NCT06613841	EARLY_PHASE1	RECRUITING	Multitracer [18F]Fluciclovine and 18F-FDG PET, and Advanced MRI for Metabolic Profiling of Glioblastoma
NCT02885272	EARLY_PHASE1	COMPLETED	FDG PET Imaging in Diagnosing Patients With Glioblastoma
NCT04825275	EARLY_PHASE1	TERMINATED	Neuro-pharmacological Properties of Repurposed Posaconazole in Glioblastoma: A Phase 0 Clinical Trial
NCT04869449	EARLY_PHASE1	TERMINATED	Neuro-pharmacological Properties of Repurposed Ketoconazole in Glioblastomas
NCT03861299	Not specified	RECRUITING	The SAFE-Trial: Awake Craniotomy Versus Surgery Under General Anesthesia for Glioblastoma Patients.
NCT05116137	Not specified	ENROLLING_BY_INVITATION	The Impact of Resistance ExerciSe on Muscle Mass in GlioblaSToma Survivors
NCT05979064	Not specified	RECRUITING	Omental Tissue Autograft in Human Recurrent Glioblastoma Multiforme (rGBM)
NCT06146725	Not specified	RECRUITING	The RESBIOP-study: Resection Versus Biopsy in High-grade Glioma Patients (ENCRAM 2202)
NCT06273176	Not specified	RECRUITING	The RECMAP-study: Resection With or Without Intraoperative Mapping for Recurrent Glioblastoma
NCT06283927	Not specified	RECRUITING	The RECSUR-study: Resection Versus Best Oncological Treatment for Recurrent Glioblastoma (ENCRAM 2302)
NCT06845020	Not specified	NOT_YET_RECRUITING	CSF Proteomic Characterization of Glioblastomas
NCT03154190	Not specified	COMPLETED	Health Care Coach Support in Reducing Acute Care Use and Cost in Patients With Cancer
NCT05801159	Not specified	COMPLETED	[18F]FPIA PET-CT in Glioblastoma Multiforme (GBM)

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
TEMOZOLOMIDE	4	2
AVELUMAB	4	1
BELINOSTAT	4	1
FLUCICLOVINE F18	4	1
LOMUSTINE	4	1
POSACONAZOLE	4	1
DISUFENTON SODIUM	3	1
HILTONOL	2	1
CHEMBL4228794	0	7
CHEMBL4248195	0	2

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 1 predictive associations from 1 curated evidence items; also 2 diagnostic, 1 oncogenic, 1 prognostic.

Molecular subtype	Therapy	Effect	Level	CIViC
BCR::NTRK2 Fusion	Entrectinib	Sensitivity/Response	CIViC C	EID12035