Pediatric angiosarcoma

Summary

Pediatric angiosarcoma (MONDO:0003022) is a disease with 2 cohort genes and 43 clinical trials. Molecularly, FLT4 Amplification confers sensitivity to Pazopanib in Angiosarcoma (CIViC Level C); 4 further subtype–drug associations are mapped below. Top therapeutic interventions include doxorubicin, ifosfamide, and dexrazoxane.

At a glance

• Cohort genes: 2
• Clinical trials: 43
• Precision-medicine evidence (CIViC): 5 subtype–drug associations

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	pediatric angiosarcoma
Mondo ID	MONDO:0003022
DOID	DOID:4505
NCIT	C9174
UMLS	C0279988
MedGen	124687
GARD	0023330
Is cancer (heuristic)	no

Also known as: angiosarcoma · angiosarcoma (disease) of childhood · childhood angiosarcoma · childhood angiosarcoma (disease) · childhood hemangiosarcoma · paediatric angiosarcoma (disease) · pediatric angiosarcoma · pediatric angiosarcoma (disease) · pediatric hemangiosarcoma

Data availability: 13 cell lines · 27 intOGen driver records.

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 angiosarcoma

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 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, pediatric hepatocellular carcinoma, 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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
KDR	Orphanet:3303	Tetralogy of Fallot

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
civic_only	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
KDR	HGNC:6307	ENSG00000128052	P35968	Vascular endothelial growth factor receptor 2	civic_evidence
PTPRB	HGNC:9665	ENSG00000127329	P23467	Receptor-type tyrosine-protein phosphatase beta	civic_evidence

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
KDR	Vascular endothelial growth factor receptor 2	Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD.
PTPRB	Receptor-type tyrosine-protein phosphatase beta	Plays an important role in blood vessel remodeling and angiogenesis.

Protein-family classification

Druggable: 2 · 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
Phosphatase	1	42.0×	0.047
Kinase	1	13.9×	0.071

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
KDR	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Tyr_kinase_rcpt_3_CS
PTPRB	Phosphatase	yes	3.1.3.48	PTP_cat, Tyr_Pase_dom, Tyr_Pase_cat

Expression context

Cohort genes with no expression data: 0.

2 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
lower lobe of lung	2
germinal epithelium of ovary	1
parietal pleura	1
endothelial cell	1
visceral pleura	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
KDR	267	broad	marker	germinal epithelium of ovary, lower lobe of lung, parietal pleura
PTPRB	258	broad	marker	endothelial cell, lower lobe of lung, visceral pleura

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
KDR	4,960
PTPRB	1,655

Intra-cohort edges

A	B	Sources
KDR	PTPRB	string_interaction

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KDR	P35968	54
PTPRB	P23467	14

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 8. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Neuropilin interactions with VEGF and VEGFR	1	1427.5×	0.004	KDR
Signaling by membrane-tethered fusions of PDGFRA or PDGFRB	1	1142.0×	0.004	KDR
VEGF binds to VEGFR leading to receptor dimerization	1	634.4×	0.004	KDR
VEGFR2 mediated cell proliferation	1	285.5×	0.007	KDR
High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells	1	80.4×	0.017	KDR
VEGFA-VEGFR2 Pathway	1	69.6×	0.017	KDR
Integrin cell surface interactions	1	67.2×	0.017	KDR
Neutrophil degranulation	1	11.5×	0.085	PTPRB

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
positive regulation of nitric oxide-cGMP mediated signal transduction	1	8426.0×	0.005	KDR
cellular response to hydrogen sulfide	1	2808.7×	0.005	KDR
post-embryonic camera-type eye morphogenesis	1	2106.5×	0.005	KDR
endocardium development	1	1685.2×	0.005	KDR
blood vessel endothelial cell differentiation	1	1685.2×	0.005	KDR
regulation of hematopoietic progenitor cell differentiation	1	1685.2×	0.005	KDR
regulation of bone development	1	1685.2×	0.005	KDR
angiogenesis	2	62.4×	0.005	KDR, PTPRB
vascular endothelial growth factor receptor-2 signaling pathway	1	1404.3×	0.005	KDR
lymph vessel development	1	936.2×	0.006	KDR
vascular wound healing	1	936.2×	0.006	KDR
positive regulation of mitochondrial depolarization	1	842.6×	0.006	KDR
epithelial cell maturation	1	766.0×	0.006	KDR
glial cell migration	1	702.2×	0.006	PTPRB
positive regulation of positive chemotaxis	1	702.2×	0.006	KDR
endothelium development	1	648.1×	0.006	KDR
positive regulation of vasculogenesis	1	648.1×	0.006	KDR
mesenchymal cell proliferation	1	561.7×	0.006	KDR
endothelial cell differentiation	1	561.7×	0.006	KDR
vascular endothelial growth factor signaling pathway	1	526.6×	0.006	KDR
phosphate-containing compound metabolic process	1	495.6×	0.006	PTPRB
embryonic hemopoiesis	1	495.6×	0.006	KDR
positive regulation of endothelial cell chemotaxis	1	495.6×	0.006	KDR
surfactant homeostasis	1	401.2×	0.007	KDR
positive regulation of mitochondrial fission	1	383.0×	0.007	KDR
positive regulation of cell migration involved in sprouting angiogenesis	1	366.4×	0.007	KDR
dephosphorylation	1	337.0×	0.007	PTPRB
positive regulation of focal adhesion assembly	1	324.1×	0.007	KDR
positive regulation of mesenchymal cell proliferation	1	300.9×	0.007	KDR
cellular response to vascular endothelial growth factor stimulus	1	280.9×	0.007	KDR

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 2 · Undrugged: 0

Druggability breadth: 2 of 2 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
KDR	VANDETANIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
KDR	172	4
PTPRB	1	2

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
VANDETANIB	4	KDR
ERLOTINIB	4	KDR
INDIGOTINDISULFONATE	4	KDR
PONATINIB	4	KDR
SORAFENIB TOSYLATE	4	KDR
PHENYL AMINOSALICYLATE	4	KDR
VEMURAFENIB	4	KDR
FEDRATINIB	4	KDR
TIVOZANIB	4	KDR
LENVATINIB	4	KDR
AXITINIB	4	KDR
SORAFENIB	4	KDR
PIPERAZINE	4	KDR
NICLOSAMIDE	4	KDR
GLAFENINE	4	KDR
SUNITINIB MALATE	4	KDR
AUROTHIOGLUCOSE	4	KDR
ALECTINIB	4	KDR
ESTRAMUSTINE PHOSPHATE	4	KDR
NERATINIB	4	KDR
INFIGRATINIB PHOSPHATE	4	KDR
INFIGRATINIB	4	KDR
IBRUTINIB	4	KDR
REGORAFENIB	4	KDR
ENTRECTINIB	4	KDR
STIRIPENTOL	4	KDR
CABOZANTINIB S-MALATE	4	KDR
QUIZARTINIB DIHYDROCHLORIDE	4	KDR
CABOZANTINIB	4	KDR
TOFACITINIB	4	KDR

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

Symbol	Assays	Type breakdown
KDR	2,687	Binding:2594, Functional:64, ADMET:27, Toxicity:2
PTPRB	36	Binding:35, ADMET:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
KDR	2.7.10.1	receptor protein-tyrosine kinase
PTPRB	3.1.3.48	protein-tyrosine-phosphatase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
KDR	2,687

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

29 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)
VANDETANIB	4	KDR
ERLOTINIB	4	KDR
INDIGOTINDISULFONATE	4	KDR
PONATINIB	4	KDR
SORAFENIB TOSYLATE	4	KDR
PHENYL AMINOSALICYLATE	4	KDR
VEMURAFENIB	4	KDR
FEDRATINIB	4	KDR
TIVOZANIB	4	KDR
LENVATINIB	4	KDR
AXITINIB	4	KDR
SORAFENIB	4	KDR
PIPERAZINE	4	KDR
NICLOSAMIDE	4	KDR
GLAFENINE	4	KDR
SUNITINIB MALATE	4	KDR
AUROTHIOGLUCOSE	4	KDR
ALECTINIB	4	KDR
ESTRAMUSTINE PHOSPHATE	4	KDR
INFIGRATINIB PHOSPHATE	4	KDR
INFIGRATINIB	4	KDR
IBRUTINIB	4	KDR
REGORAFENIB	4	KDR
ENTRECTINIB	4	KDR
STIRIPENTOL	4	KDR
CABOZANTINIB S-MALATE	4	KDR
QUIZARTINIB DIHYDROCHLORIDE	4	KDR
CABOZANTINIB	4	KDR
TOFACITINIB	4	KDR

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	KDR
B	Phased (≥1) drug, not yet approved	1	PTPRB
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: 43.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	24
Not specified	8
PHASE1	6
PHASE3	2
PHASE1/PHASE2	2
PHASE4	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02625389	PHASE4	COMPLETED	A Study to Evaluate How Safe and Effective is the Mixture of Lipiodol® Ultra Fluid and Glue When Used for Embolization Procedures
NCT00346164	PHASE3	COMPLETED	Observation, Radiation Therapy, Combination Chemotherapy, and/or Surgery in Treating Young Patients With Soft Tissue Sarcoma
NCT02979899	PHASE3	COMPLETED	Trial of TRC105 and Pazopanib Versus Pazopanib Alone in Patients With Advanced Angiosarcoma
NCT01042379	PHASE2	RECRUITING	I-SPY TRIAL: Neoadjuvant and Personalized Adaptive Novel Agents to Treat Breast Cancer
NCT02834013	PHASE2	ACTIVE_NOT_RECRUITING	Nivolumab and Ipilimumab in Treating Patients With Rare Tumors
NCT03331250	PHASE2	ACTIVE_NOT_RECRUITING	Eribulin in Angiosarcoma and Epithelioid Hemangioendothelioma (EHE)
NCT04668300	PHASE2	ACTIVE_NOT_RECRUITING	Oleclumab and Durvalumab for the Treatment of Recurrent, Refractory, or Metastatic Sarcoma
NCT05961761	PHASE2	RECRUITING	Propranolol and Pembrolizumab in Advanced Soft Tissue Sarcoma Patients
NCT06239272	PHASE1/PHASE2	RECRUITING	NRSTS2021, A Risk Adapted Study Evaluating Maintenance Pazopanib, Limited Margin, Dose-Escalated Radiation Therapy and Selinexor in Non-Rhabdomyosarcoma Soft Tissue Sarcoma (NRSTS)
NCT06277154	PHASE2	RECRUITING	MASCT-I Combined With Doxorubicin and Ifosfamide for First-line Treatment of Advanced Soft Tissue Sarcoma
NCT06638931	PHASE2	RECRUITING	Agnostic Therapy in Rare Solid Tumors
NCT06673628	PHASE2	RECRUITING	Pembrolizumab Plus Lenvatinib in Unresectable Cutaneous Angiosarcoma Patients
NCT06849986	PHASE2	RECRUITING	IO Combined With AI as First-line Treatment for Patients With Soft Tissue Sarcoma(TAIS)
NCT06898970	PHASE2	ACTIVE_NOT_RECRUITING	Intratumoral Vusolimogene Oderparepvec (VO) in Combination With Pembrolizumab for Angiosarcoma
NCT00887809	PHASE2	COMPLETED	Gemcitabine and Docetaxel With Bevacizumab in Selected Sarcoma Subtypes
NCT01055028	PHASE2	TERMINATED	Paclitaxel + Bevacizumab (Avastin) for the Treatment of Metastatic or Unresectable Angiosarcoma
NCT01303497	PHASE2	COMPLETED	Efficacity of Weekly Paclitaxel in Association or Not With Bevacizumab in Metastatic or Locally Advanced Angiosarcomas
NCT01614795	PHASE2	COMPLETED	Cixutumumab and Temsirolimus in Treating Younger Patients With Recurrent or Refractory Sarcoma
NCT02212015	PHASE2	TERMINATED	Evaluation of Votrient in Angiosarcoma
NCT02584309	PHASE2	COMPLETED	Doxorubicin With Upfront Dexrazoxane for the Treatment of Advanced or Metastatic Soft Tissue Sarcoma
NCT02732678	PHASE1/PHASE2	UNKNOWN	Dose-Finding of Propranolol in Combination With Metronomic Fixed Oral Cyclophosphamide Based on Bivariate Efficacy-tolerability Outcome in Patients With Locally Advanced or Metastatic Angiosarcoma: A Collaborative and Innovative Phase I-II Sequential Trial by the French Sarcoma Group (GSF/GETO)
NCT03512834	PHASE2	UNKNOWN	Paclitaxel-Avelumab for Angiosarcoma
NCT04518124	PHASE2	COMPLETED	Propranolol in Angiosarcoma
NCT04607200	PHASE2	WITHDRAWN	AGEN2034 & AGEN1884 in Patients With Recurrent, Inoperable Angiosarcoma
NCT04859465	PHASE2	UNKNOWN	Albumin-bound Paclitaxel Combined With Liposomal Doxorubicin in the Treatment of Advanced or Unresectable Angiosarcoma
NCT04873375	PHASE2	COMPLETED	Cemiplimab for Secondary Angiosarcomas
NCT04906876	PHASE2	WITHDRAWN	A Phase 2 Study of 9-ING-41Combined With Chemotherapy in Adolescents and Adults With Advanced Sarcomas
NCT05026736	PHASE2	TERMINATED	Sintilimab for the Treatment of Locally Advanced, Metastatic, or Recurrent Angiosarcoma, the SiARa Cancer Study
NCT05116800	PHASE2	WITHDRAWN	Phase 2 Study of 9-ING-41 With Chemotherapy in Sarcoma
NCT03860272	PHASE1	ACTIVE_NOT_RECRUITING	Fc-Engineered Anti-CTLA-4 Monoclonal Antibody in Advanced Cancer
NCT05859074	PHASE1	RECRUITING	A Study of MQ710 With and Without Pembrolizumab in People With Solid Tumor Cancer
NCT06440005	PHASE1	RECRUITING	A Study to Evaluate Safety, Tolerability and Preliminary Activity of AGX101 in Participants With Advanced Solid Tumors
NCT00720174	PHASE1	COMPLETED	Cixutumumab and Doxorubicin Hydrochloride in Treating Patients With Unresectable, Locally Advanced, or Metastatic Soft Tissue Sarcoma
NCT03009201	PHASE1	COMPLETED	Ribociclib and Doxorubicin in Treating Patients With Metastatic or Advanced Soft Tissue Sarcomas That Cannot Be Removed by Surgery
NCT05799612	PHASE1	WITHDRAWN	Phase I Study of TH1 Dendritic Cell Immunotherapy for the Treatment of Cutaneous Angiosarcoma
NCT04055220	Not specified	RECRUITING	Efficacy and Safety of Regorafenib as Maintenance Therapy After First-line Treatment in Patients With Bone Sarcomas
NCT06375941	Not specified	RECRUITING	Prospective Observational Study of Localized Angiosarcoma of Any Site: ProStars
NCT06526897	Not specified	NOT_YET_RECRUITING	Evaluation of Chest CT Versus Chest X-Ray for Lung Surveillance After Curative-Intent Resection of High-Risk Truncal-Extremity Soft Tissue Sarcoma
NCT07432932	Not specified	RECRUITING	Precision Medicine Approaches for Neoadjuvant Therapy in High-risk Sarcoma Patients
NCT01567046	Not specified	COMPLETED	Studying Genes in Tissue Samples From Younger and Adolescent Patients With Soft Tissue Sarcomas

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
DOXORUBICIN	4	6
IFOSFAMIDE	4	4
DEXRAZOXANE	4	3
PAZOPANIB	4	3
CEMIPLIMAB	4	2
ABEMACICLIB	4	1
AVELUMAB	4	1
DOSTARLIMAB	4	1
DURVALUMAB	4	1
ERIBULIN	4	1
LASOFOXIFENE	4	1
NERATINIB	4	1
NIRAPARIB	4	1
PERTUZUMAB	4	1
PEXIDARTINIB	4	1
SARILUMAB	4	1
SELINEXOR	4	1
TRASTUZUMAB EMTANSINE	4	1
ZANIDATAMAB	4	1
BALSTILIMAB	3	2
AFIMOXIFENE	3	1
AMCENESTRANT	3	1
BOTENSILIMAB	3	1
CAROTUXIMAB	3	1
DATOPOTAMAB DERUXTECAN	3	1
ENCEQUIDAR	3	1
ENDOXIFEN	3	1
GANETESPIB	3	1
IVONESCIMAB	3	1
OLECLUMAB	3	1

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 5 predictive associations from 5 curated evidence items; also 1 diagnostic.

Molecular subtype	Therapy	Effect	Level	CIViC
FLT4 Amplification	Pazopanib	Sensitivity/Response	CIViC C	EID5911
KDR Amplification	Pazopanib	Sensitivity/Response	CIViC C	EID7139
KDR A1065T	Sorafenib + Sunitinib	Sensitivity/Response	CIViC D	EID1106
KDR D717V	Sorafenib + Sunitinib	Sensitivity/Response	CIViC D	EID1107
PTPRB Loss-of-function	Vatalanib + Sunitinib	Sensitivity/Response	CIViC D	EID1895