Pediatric hepatocellular carcinoma

Summary

Pediatric hepatocellular carcinoma (MONDO:0018055) is a cancer with 1 cohort gene and 102 clinical trials. Top therapeutic interventions include sorafenib, chlorotrianisene, and irinotecan.

At a glance

• Classification: Cancer
• Prevalence: 1-9 / 1 000 000 (Europe) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 3
• Phenotypes (HPO): 9
• Clinical trials: 102

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Annual incidence	1-9 / 1 000 000	0.15	Europe	Validated
Annual incidence	<1 / 1 000 000		United States	Validated

Signs & symptoms

Clinical features (HPO)

9 HPO clinical features (Orphanet curated; top 9 by frequency):

HPO ID	Term	Frequency
HP:0001395	Hepatic fibrosis	Very frequent (80-99%)
HP:0002027	Abdominal pain	Very frequent (80-99%)
HP:0002240	Hepatomegaly	Very frequent (80-99%)
HP:0006254	Elevated alpha-fetoprotein	Very frequent (80-99%)
HP:0002013	Vomiting	Frequent (30-79%)
HP:0002605	Hepatic necrosis	Frequent (30-79%)
HP:0012378	Fatigue	Frequent (30-79%)
HP:0030242	Portal vein thrombosis	Frequent (30-79%)
HP:0410019	Epigastric pain	Frequent (30-79%)

Identifiers

Disease identifiers

Field	Value
Canonical name	pediatric hepatocellular carcinoma
Mondo ID	MONDO:0018055
Orphanet	33402
DOID	DOID:0070322
NCIT	C7955
UMLS	C0279606
MedGen	75999
GARD	0009331
Is cancer (heuristic)	yes

Also known as: childhood carcinoma of liver cell · childhood carcinoma of the liver cell · childhood hepatocellular carcinoma · childhood hepatoma · childhood liver cell carcinoma · childhood-onset HCC · childhood-onset hepatocellular carcinoma · hepatocellular cancer · paediatric carcinoma of liver cell · Paediatric carcinoma of the liver cell · paediatric HCC · paediatric hepatoma · paediatric liver cell carcinoma · pediatric carcinoma of liver cell · Pediatric carcinoma of the liver cell · pediatric HCC · pediatric hepatoma · pediatric liver cell carcinoma

Data availability: 3 ClinVar variants · 19 cell lines.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › cancer › childhood malignant neoplasm › pediatric hepatocellular carcinoma

Related subtypes (29): childhood oligodendroglioma, pediatric osteosarcoma, pediatric fibrosarcoma, childhood choroid plexus carcinoma, childhood central nervous system primitive neuroectodermal neoplasm, childhood brain stem neoplasm, pediatric angiosarcoma, pediatric mesenchymal chondrosarcoma, pediatric liposarcoma, pediatric lymphoma, childhood malignant mesenchymoma, pediatric myxoid chondrosarcoma, childhood botryoid rhabdomyosarcoma, pediatric intraocular retinoblastoma, childhood cerebral astrocytoma, childhood epithelioid sarcoma, childhood pleomorphic rhabdomyosarcoma, pediatric infratentorial ependymoma, pediatric supratentorial ependymoma, childhood malignant schwannoma, pediatric extraocular retinoblastoma, childhood leukemia, childhood precursor T-lymphoblastic lymphoma/leukemia, malignant childhood germ cell neoplasm, pleuropulmonary blastoma, childhood malignant kidney neoplasm, childhood malignant melanoma, extrarenal rhabdoid tumor, pediatric high-grade glioma

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

ClinVar germline variants

3 retrieved; paginated sample, class counts are floors:

2 pathogenic, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
13889	NM_000245.4(MET):c.3750G>A (p.Met1250Ile)	MET	Pathogenic	no assertion criteria provided
13890	NM_000245.4(MET):c.3731A>G (p.Lys1244Arg)	MET	Pathogenic	no assertion criteria provided
13888	NM_000245.4(MET):c.3518C>T (p.Thr1173Ile)	MET	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 5 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MET	Orphanet:319298	Papillary renal cell carcinoma
MET	Orphanet:33402	Pediatric hepatocellular carcinoma
MET	Orphanet:47044	Hereditary papillary renal cell carcinoma
MET	Orphanet:488265	Osteofibrous dysplasia
MET	Orphanet:90636	Rare autosomal recessive non-syndromic sensorineural deafness type DFNB

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
MET	HGNC:7029	ENSG00000105976	P08581	Hepatocyte growth factor receptor	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MET	Hepatocyte growth factor receptor	Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to hepatocyte growth factor/HGF ligand.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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	27.7×	0.036

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MET	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Semap_dom

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cartilage tissue	1
germinal epithelium of ovary	1
pigmented layer of retina	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MET	270	ubiquitous	marker	pigmented layer of retina, germinal epithelium of ovary, cartilage tissue

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MET	5,823

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MET	P08581	130

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 44. Enrichment computed across 1 evidence-associated genes (1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Drug-mediated inhibition of MET activation	1	5710.0×	0.004	MET
MET activates STAT3	1	3806.7×	0.004	MET
MET activates PTPN11	1	2284.0×	0.004	MET
MET interacts with TNS proteins	1	2284.0×	0.004	MET
MET Receptor Activation	1	1903.3×	0.004	MET
MET activates PI3K/AKT signaling	1	1903.3×	0.004	MET
Sema4D mediated inhibition of cell attachment and migration	1	1427.5×	0.004	MET
MET receptor recycling	1	1142.0×	0.004	MET
MET activates RAS signaling	1	1038.2×	0.004	MET
MET activates RAP1 and RAC1	1	1038.2×	0.004	MET
Listeria monocytogenes entry into host cells	1	1038.2×	0.004	MET
InlB-mediated entry of Listeria monocytogenes into host cell	1	761.3×	0.005	MET
Sema4D in semaphorin signaling	1	671.8×	0.005	MET
MET promotes cell motility	1	601.0×	0.005	MET
MECP2 regulates neuronal receptors and channels	1	601.0×	0.005	MET
Regulation of MITF-M-dependent genes involved in cell cycle and proliferation	1	571.0×	0.005	MET
Negative regulation of MET activity	1	519.1×	0.005	MET
Semaphorin interactions	1	393.8×	0.006	MET
MET activates PTK2 signaling	1	380.7×	0.006	MET
PI3K/AKT Signaling in Cancer	1	368.4×	0.006	MET
Bacterial Infection Pathways	1	335.9×	0.006	MET
Signaling by MET	1	317.2×	0.006	MET
Transcriptional Regulation by MECP2	1	317.2×	0.006	MET
Negative regulation of the PI3K/AKT network	1	278.5×	0.007	MET
MITF-M-dependent gene expression	1	181.3×	0.010	MET
MAPK1/MAPK3 signaling	1	131.3×	0.013	MET
Constitutive Signaling by Aberrant PI3K in Cancer	1	126.9×	0.013	MET
MITF-M-regulated melanocyte development	1	114.2×	0.014	MET
MAPK family signaling cascades	1	102.9×	0.015	MET
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	1	96.8×	0.015	MET

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
negative regulation of hydrogen peroxide-mediated programmed cell death	1	4213.0×	0.003	MET
hepatocyte growth factor receptor signaling pathway	1	2106.5×	0.003	MET
endothelial cell morphogenesis	1	1053.2×	0.003	MET
positive regulation of endothelial cell chemotaxis	1	991.3×	0.003	MET
positive chemotaxis	1	802.5×	0.003	MET
branching morphogenesis of an epithelial tube	1	732.7×	0.003	MET
pancreas development	1	674.1×	0.003	MET
excitatory postsynaptic potential	1	443.5×	0.004	MET
semaphorin-plexin signaling pathway	1	401.2×	0.004	MET
negative regulation of autophagy	1	259.3×	0.006	MET
liver development	1	221.7×	0.006	MET
cell surface receptor protein tyrosine kinase signaling pathway	1	173.7×	0.007	MET
neuron differentiation	1	100.3×	0.012	MET
cell surface receptor signaling pathway	1	64.1×	0.017	MET
positive regulation of transcription by RNA polymerase II	1	14.9×	0.067	MET

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 0

Druggability breadth: 1 of 1 evidence-associated genes (100%) 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
MET	AFATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MET	95	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
AFATINIB	4	MET
FEDRATINIB	4	MET
TIVOZANIB	4	MET
AXITINIB	4	MET
SORAFENIB	4	MET
NERATINIB	4	MET
INFIGRATINIB PHOSPHATE	4	MET
INFIGRATINIB	4	MET
PALBOCICLIB	4	MET
ENTRECTINIB	4	MET
DABRAFENIB	4	MET
CABOZANTINIB S-MALATE	4	MET
AFATINIB DIMALEATE	4	MET
CABOZANTINIB	4	MET
CERITINIB	4	MET
VANDETANIB	4	MET
BOSUTINIB	4	MET
CAPMATINIB	4	MET
TEPOTINIB	4	MET
BRIGATINIB	4	MET
ENSARTINIB	4	MET
PAZOPANIB	4	MET
NINTEDANIB	4	MET
SUNITINIB	4	MET
ERLOTINIB	4	MET
CRIZOTINIB	4	MET
MIDOSTAURIN	4	MET
GEFITINIB	4	MET
LINSITINIB	3	MET
RIGOSERTIB	3	MET

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
MET	2,015	Binding:2005, Functional:6, ADMET:4

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
MET	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
MET	2,015

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

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

Drug repurposing candidates

28 approved/phased drugs hit cohort targets but don’t yet appear in disease-level clinical trials. Target-inhibition rationale is strongest for cancer driver genes; a bioactivity hit is a screening signal, not a treatment claim.

Compound	Max phase	Cohort target (bioactivity)
AFATINIB	4	MET
FEDRATINIB	4	MET
AXITINIB	4	MET
NERATINIB	4	MET
INFIGRATINIB PHOSPHATE	4	MET
INFIGRATINIB	4	MET
PALBOCICLIB	4	MET
ENTRECTINIB	4	MET
DABRAFENIB	4	MET
CABOZANTINIB S-MALATE	4	MET
AFATINIB DIMALEATE	4	MET
CABOZANTINIB	4	MET
CERITINIB	4	MET
VANDETANIB	4	MET
BOSUTINIB	4	MET
CAPMATINIB	4	MET
TEPOTINIB	4	MET
BRIGATINIB	4	MET
ENSARTINIB	4	MET
PAZOPANIB	4	MET
NINTEDANIB	4	MET
SUNITINIB	4	MET
ERLOTINIB	4	MET
CRIZOTINIB	4	MET
MIDOSTAURIN	4	MET
GEFITINIB	4	MET
LINSITINIB	3	MET
RIGOSERTIB	3	MET

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	MET
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	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 102.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	45
PHASE2	25
PHASE1	18
PHASE1/PHASE2	9
PHASE4	3
PHASE2/PHASE3	1
PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05185505	PHASE4	RECRUITING	Atezolizumab and Bevacizumab Pre-Liver Transplantation for Patients With Hepatocellular Carcinoma Beyond Milan Criteria
NCT01849588	PHASE4	TERMINATED	HCV-RNA Kinetics During Sorafenib for Hepatocellular Carcinoma (HCC)
NCT03151213	PHASE4	COMPLETED	Effect of Pregabalin on the Postoperative Analgesia in RFA of Focal Lesions in the Liver
NCT03533582	PHASE3	ACTIVE_NOT_RECRUITING	Cisplatin and Combination Chemotherapy in Treating Children and Young Adults With Hepatoblastoma or Liver Cancer After Surgery
NCT01655641	PHASE2/PHASE3	UNKNOWN	Study of Tranexamic Acid for Reducing Blood Requirement in Patients Undergoing Major Gastro-intestinal Surgery
NCT03937830	PHASE2	ACTIVE_NOT_RECRUITING	Combined Treatment of Durvalumab, Bevacizumab, Tremelimumab and Transarterial Chemoembolization (TACE) in Subjects With Hepatocellular Carcinoma or Biliary Tract Carcinoma
NCT04912765	PHASE2	RECRUITING	Neoantigen Dendritic Cell Vaccine and Nivolumab in HCC and Liver Metastases From CRC
NCT05438420	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Oral Axl/Mer/CSF1R Selective Tyrosine Kinase Inhibitor Q702 in Combination With Pembrolizumab in Patients With Selected Advanced Solid Tumors
NCT05451043	PHASE2	RECRUITING	Durvalumab and Tremelimumab in Combination With Propranolol and Chemotherapy for Treatment of Advanced Hepatopancreabiliary Tumors (BLOCKED)
NCT05992220	PHASE2	RECRUITING	Atezolizumab Plus Bevacizumab Alone or Combined with External Beam Radiotherapy for HCC with Macrovascular Invasion
NCT06239194	PHASE1/PHASE2	RECRUITING	Dose Escalation and Dose Expansion Study of MDX2001 in Patients With Advanced Solid Tumors
NCT06362369	PHASE1/PHASE2	RECRUITING	A Study of Oral 7HP349 (Alintegimod) in Combination With Ipilimumab Followed by Nivolumab Monotherapy
NCT06935175	PHASE2	NOT_YET_RECRUITING	A Study of SHR-1826 Monotherapy or in Combination With Immunotherapy in the Treatment of Advanced Hepatocellular Cancer
NCT07227012	PHASE1/PHASE2	RECRUITING	Symbiotic-GI-13: A Study to Learn About Study Medicine Called PF-08634404 as a Single Treatment and Combination Treatment in Adult Participants With a Liver Cancer Called Hepatocellular Carcinoma, That is Too Advanced to be Removed by Surgery and May Have Spread to Other Parts of the Body.
NCT00091182	PHASE2	COMPLETED	Oxaliplatin in Treating Young Patients With Recurrent Solid Tumors That Have Not Responded to Previous Treatment
NCT00813293	PHASE2	COMPLETED	Sorafenib Therapy Prior to Radiofrequency Ablation for Intermediate Sized Hepatocellular Cancer
NCT00878215	PHASE2	TERMINATED	Clinical Application of Image-Guided Liver Surgery
NCT01375569	PHASE2	COMPLETED	TRC105 for Liver Cancer That Has Not Responded to Sorafenib
NCT01502410	PHASE2	COMPLETED	Sorafenib Tosylate in Treating Younger Patients With Relapsed or Refractory Rhabdomyosarcoma, Wilms Tumor, Liver Cancer, or Thyroid Cancer
NCT01522937	PHASE2	COMPLETED	A Study of Individualized Stereotactic Body Radiation Therapy (SBRT) for Intrahepatic Cancer
NCT01775501	PHASE2	COMPLETED	Sorafenib + mFOLFOX for Hepatocellular Carcinoma
NCT01807156	PHASE2	TERMINATED	Phase II Trial of Tivozanib in Advanced Hepatocellular Cancer
NCT01967823	PHASE2	COMPLETED	T Cell Receptor Immunotherapy Targeting NY-ESO-1 for Patients With NY-ESO-1 Expressing Cancer
NCT02042443	PHASE2	COMPLETED	Trametinib or Combination Chemotherapy in Treating Patients With Refractory or Advanced Biliary or Gallbladder Cancer or That Cannot Be Removed by Surgery
NCT02082210	PHASE1/PHASE2	COMPLETED	A Study of Emibetuzumab in Combination With Ramucirumab (LY3009806) in Participants With Advanced Cancer
NCT02141906	PHASE2	COMPLETED	A Pilot Study of OncozeneTM Microspheres for Intra-arterial Delivery of Doxorubicin
NCT02528526	PHASE1/PHASE2	UNKNOWN	Effects of OXY111A in Primary and Secondary Hepato-Pancreato-Biliary Neoplasm
NCT02958163	PHASE2	TERMINATED	Clinical Trial Comparing TACE With TACE + SABR in Stage BCLC B HCC (HepSTAR)
NCT03026803	PHASE2	TERMINATED	A Study of Oxaliplatin and Capecitabine in Unresectable Metastatic Hepatocellular Cancer
NCT03037437	PHASE2	COMPLETED	Sorafenib Induced Autophagy Using Hydroxychloroquine in Hepatocellular Cancer
NCT03480152	PHASE1/PHASE2	TERMINATED	Messenger RNA (mRNA)-Based, Personalized Cancer Vaccine Against Neoantigens Expressed by the Autologous Cancer
NCT03572582	PHASE2	COMPLETED	Transarterial Chemoembolization in Combination With Nivolumab Performed for Intermediate Stage Hepatocellular Carcinoma
NCT03785210	PHASE2	TERMINATED	Nivolumab (Anti-PD1), Tadalafil and Oral Vancomycin in People With Refractory Primary Hepatocellular Carcinoma or Liver Dominant Metastatic Cancer From Colorectal or Pancreatic Cancers
NCT03971201	PHASE2	UNKNOWN	A Randomized Phase II Trial of Surgery Plus Sorafenib vs. Sorafenib Alone for Hepatocellular Cancer (HCC) With Portal Vein Invasion
NCT04033107	PHASE2	UNKNOWN	High Dose Vitamin C Combined With Metformin in the Treatment of Malignant Tumors
NCT05070247	PHASE1/PHASE2	TERMINATED	A Study of TAK-500 With or Without Pembrolizumab in Adults With Select Locally Advanced or Metastatic Solid Tumors
NCT05453383	PHASE2	UNKNOWN	Clinical Recruitment of Patients With First-line Targeted Drug Resistance or Intolerance to Hepatocellular Cancer With PD-1 Inhibitor (Toripalimab,JS001) Detected on the NGS Platform Combined With Anlotinib
NCT05497453	PHASE1/PHASE2	TERMINATED	A Phase 1/2 Study to Evaluate OTX-2002 in Patients with Hepatocellular Carcinoma and Other Solid Tumor Types Known for Association with the MYC Oncogene
NCT06690281	PHASE2	WITHDRAWN	A Phase II Study of Adjuvant Immunotherapy Targeting KRAS G12D, KRAS G12V, or TP53 R175H for Participants With Advanced Gastrointestinal Malignancies
NCT03132792	PHASE1	ACTIVE_NOT_RECRUITING	AFPᶜ³³²T in Advanced HCC

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
SORAFENIB	4	13
CHLOROTRIANISENE	4	2
IRINOTECAN	4	2
TIVOZANIB	4	2
ATEZOLIZUMAB	4	1
BEVACIZUMAB	4	1
DEXAMETHASONE	4	1
FERUMOXYTOL	4	1
PREGABALIN	4	1
RAMUCIRUMAB	4	1
TRAMETINIB	4	1
CAROTUXIMAB	3	1
NISEVOKITUG	3	1
SASANLIMAB	3	1
SPARTALIZUMAB	3	1
ALINTEGIMOD	2	1
C-188-9	2	1
CARMOFUR	2	1
EMIBETUZUMAB	2	1
LORIGERLIMAB	2	1
VOBRAMITAMAB DUOCARMAZINE	2	1
YTTRIUM Y-90	2	1
CHEMBL5412235	0	1
CHEMBL5433950	0	1
S-ROLIPRAM	0	1