Pediatric osteosarcoma

Summary

Pediatric osteosarcoma (MONDO:0002623) is a disease with 4 cohort genes and 323 clinical trials. Molecularly, ERCC2 K751Q is associated with resistance to Cisplatin in Osteosarcoma (CIViC Level B); 4 further subtype–drug associations are mapped below. Top therapeutic interventions include mifamurtide acid, cabozantinib, and dexrazoxane.

At a glance

• Cohort genes: 4
• Clinical trials: 323
• 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 osteosarcoma
Mondo ID	MONDO:0002623
DOID	DOID:3361
NCIT	C6585
UMLS	C1332986
MedGen	272464
Is cancer (heuristic)	no

Also known as: childhood osteogenic sarcoma · childhood osteosarcoma · childhood osteosarcoma (disease) · osteosarcoma · osteosarcoma (disease) of childhood · paediatric osteosarcoma (disease) · pediatric osteosarcoma · pediatric osteosarcoma (disease)

Data availability: 803 cell lines · 14 intOGen driver records.

Disease family

An umbrella term covering 3 Mondo subtypes.

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

Related subtypes (29): childhood oligodendroglioma, 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, pediatric hepatocellular carcinoma, childhood malignant kidney neoplasm, childhood malignant melanoma, extrarenal rhabdoid tumor, pediatric high-grade glioma

Subtypes (3): childhood parosteal osteosarcoma, childhood extraosseous osteosarcoma, childhood intracortical osteosarcoma

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: 33 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TP53	Orphanet:1333	Familial pancreatic carcinoma
TP53	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
TP53	Orphanet:1501	Adrenocortical carcinoma
TP53	Orphanet:210159	Adult hepatocellular carcinoma
TP53	Orphanet:251576	Gliosarcoma
TP53	Orphanet:251579	Giant cell glioblastoma
TP53	Orphanet:251899	Choroid plexus carcinoma
TP53	Orphanet:2807	Papilloma of choroid plexus
TP53	Orphanet:293199	Pleomorphic rhabdomyosarcoma
TP53	Orphanet:3318	Essential thrombocythemia
TP53	Orphanet:524	Li-Fraumeni syndrome
TP53	Orphanet:52688	Myelodysplastic syndrome
TP53	Orphanet:585909	B-lymphoblastic leukemia/lymphoma with t(9;22)(q34.1;q11.2)
TP53	Orphanet:667662	Breast implant-associated anaplastic large cell lymphoma
TP53	Orphanet:668	Osteosarcoma
TP53	Orphanet:67038	B-cell chronic lymphocytic leukemia
TP53	Orphanet:70573	Small cell lung cancer
TP53	Orphanet:96253	Cushing disease
TP53	Orphanet:99756	Alveolar rhabdomyosarcoma
TP53	Orphanet:99757	Embryonal rhabdomyosarcoma
ERCC2	Orphanet:1466	COFS syndrome
ERCC2	Orphanet:220295	Xeroderma pigmentosum-Cockayne syndrome complex
ERCC2	Orphanet:33364	Trichothiodystrophy
ERCC2	Orphanet:910	Xeroderma pigmentosum
ATRX	Orphanet:100075	Neuroendocrine tumor of stomach
ATRX	Orphanet:231401	Alpha-thalassemia-myelodysplastic syndrome
ATRX	Orphanet:847	X-linked alpha-thalassemia-intellectual disability syndrome
ATRX	Orphanet:96253	Cushing disease
RB1	Orphanet:1587	Monosomy 13q14 syndrome
RB1	Orphanet:357027	Hereditary retinoblastoma
RB1	Orphanet:357034	Non-hereditary retinoblastoma
RB1	Orphanet:668	Osteosarcoma
RB1	Orphanet:70573	Small cell lung cancer

Cohort genes → proteins

4 cohort genes, 4 distinct canonical proteins.

Evidence partition

Subset	Genes
civic_only	4

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TP53	HGNC:11998	ENSG00000141510	P04637	Cellular tumor antigen p53	civic_evidence
ERCC2	HGNC:3434	ENSG00000104884	P18074	General transcription and DNA repair factor IIH helicase subunit XPD	civic_evidence
ATRX	HGNC:886	ENSG00000085224	P46100	Transcriptional regulator ATRX	civic_evidence
RB1	HGNC:9884	ENSG00000139687	P06400	Retinoblastoma-associated protein	civic_evidence

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TP53	Cellular tumor antigen p53	Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence.
ERCC2	General transcription and DNA repair factor IIH helicase subunit XPD	ATP-dependent 5’-3’ DNA helicase.
ATRX	Transcriptional regulator ATRX	Involved in transcriptional regulation and chromatin remodeling.
RB1	Retinoblastoma-associated protein	Tumor suppressor that is a key regulator of the G1/S transition of the cell cycle.

Protein-family classification

Druggable: 1 · Difficult: 2 · Unknown: 1 · Druggable fraction: 0.25

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
Transcription factor	2	4.1×	0.223
Enzyme (other)	1	3.0×	0.441
Other/Unknown	1	0.5×	0.962

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TP53	Transcription factor	no		p53_tumour_suppressor, p53-like_TF_DNA-bd_sf, p53_tetrameristn
ERCC2	Enzyme (other)	yes	3.6.4.12	RAD3/XPD, DNA/RNA_helicase_DEAH_CS, Helicase-like_DEXD_c2
ATRX	Transcription factor	no		SNF2_N, Helicase_C-like, Znf_FYVE_PHD
RB1	Other/Unknown	no		RB_B, RB_A, Cyclin-like_dom

Expression context

Cohort genes with no expression data: 0.

4 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)	4
unknown	0

Top tissues across cohort

Tissue	Cohort genes
ganglionic eminence	1
tendon of biceps brachii	1
ventricular zone	1
left adrenal gland	1
right adrenal gland	1
stromal cell of endometrium	1
calcaneal tendon	1
colonic epithelium	1
endothelial cell	1
choroid plexus epithelium	1
epithelium of nasopharynx	1
visceral pleura	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TP53	223	ubiquitous	marker	ventricular zone, ganglionic eminence, tendon of biceps brachii
ERCC2	184	ubiquitous	marker	stromal cell of endometrium, right adrenal gland, left adrenal gland
ATRX	294	ubiquitous	marker	endothelial cell, calcaneal tendon, colonic epithelium
RB1	287	ubiquitous	marker	epithelium of nasopharynx, choroid plexus epithelium, visceral pleura

Protein interactions among cohort

Intra-cohort edges: 2.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TP53	22,736
ATRX	5,796
RB1	4,374
ERCC2	2,746

Intra-cohort edges

A	B	Sources
ATRX	TP53	string_interaction
RB1	TP53	string_interaction

Structural data

PDB: 4 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TP53	P04637	313
ERCC2	P18074	51
RB1	P06400	19
ATRX	P46100	12

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 102. Enrichment computed across 4 evidence-associated genes (4 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 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Formation of Senescence-Associated Heterochromatin Foci (SAHF)	2	335.9×	0.001	TP53, RB1
Oncogene Induced Senescence	2	167.9×	0.003	TP53, RB1
Alternative Lengthening of Telomeres (ALT)	1	2855.0×	0.004	ATRX
Defective translocation of RB1 mutants to the nucleus	1	2855.0×	0.004	RB1
Defective Inhibition of DNA Recombination at Telomere	1	2855.0×	0.004	ATRX
Diseases of Telomere Maintenance	1	2855.0×	0.004	ATRX
Loss of function of TP53 in cancer due to loss of tetramerization ability	1	2855.0×	0.004	TP53
TP53 Regulates Transcription of DNA Repair Genes	2	90.6×	0.004	TP53, ERCC2
Regulation of TP53 Expression	1	1427.5×	0.006	TP53
Defective Inhibition of DNA Recombination at Telomere Due to DAXX Mutations	1	1427.5×	0.006	ATRX
Defective Inhibition of DNA Recombination at Telomere Due to ATRX Mutations	1	1427.5×	0.006	ATRX
Phosphorylation of proteins involved in G1/S transition by active Cyclin E:Cdk2 complexes	1	713.8×	0.010	RB1
Transcriptional activation of cell cycle inhibitor p21	1	713.8×	0.010	TP53
Replication of the SARS-CoV-1 genome	1	713.8×	0.010	RB1
Replication of the SARS-CoV-2 genome	1	713.8×	0.010	RB1
Activation of NOXA and translocation to mitochondria	1	475.8×	0.013	TP53
RUNX3 regulates CDKN1A transcription	1	407.9×	0.015	TP53
PI5P Regulates TP53 Acetylation	1	317.2×	0.018	TP53
Activation of PUMA and translocation to mitochondria	1	285.5×	0.019	TP53
TP53 Regulates Transcription of Caspase Activators and Caspases	1	237.9×	0.019	TP53
TP53 Regulates Transcription of Death Receptors and Ligands	1	237.9×	0.019	TP53
Positive Regulation of CDH1 Gene Transcription	1	237.9×	0.019	RB1
Urea cycle	1	219.6×	0.019	TP53
Inhibition of replication initiation of damaged DNA by RB1/E2F1	1	203.9×	0.019	RB1
Regulation of TP53 Activity through Association with Co-factors	1	203.9×	0.019	TP53
Cytosolic iron-sulfur cluster assembly	1	190.3×	0.019	ERCC2
TP53 regulates transcription of several additional cell death genes whose specific roles in p53-dependent apoptosis remain uncertain	1	190.3×	0.019	TP53
Stabilization of p53	1	190.3×	0.019	TP53
TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest	1	178.4×	0.020	TP53
Zygotic genome activation (ZGA)	1	167.9×	0.020	TP53

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 4 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 glial cell proliferation	2	842.6×	2e-04	TP53, RB1
multicellular organism growth	3	102.8×	2e-04	TP53, ERCC2, ATRX
glial cell proliferation	2	443.5×	5e-04	TP53, RB1
hematopoietic stem cell differentiation	2	383.0×	5e-04	TP53, ERCC2
transcription by RNA polymerase II	3	52.9×	5e-04	ERCC2, ATRX, RB1
chromosome organization	2	290.6×	5e-04	TP53, RB1
intrinsic apoptotic signaling pathway by p53 class mediator	2	290.6×	5e-04	TP53, ERCC2
embryonic organ development	2	240.7×	6e-04	TP53, ERCC2
determination of adult lifespan	2	216.1×	7e-04	TP53, ERCC2
nucleotide-excision repair	2	191.5×	8e-04	TP53, ERCC2
DNA damage response, signal transduction by p53 class mediator	2	179.3×	8e-04	TP53, ATRX
cellular response to xenobiotic stimulus	2	120.4×	0.002	TP53, RB1
regulation of DNA-templated transcription	3	23.7×	0.002	TP53, ATRX, RB1
Ras protein signal transduction	2	102.8×	0.002	TP53, RB1
neuron apoptotic process	2	92.6×	0.002	TP53, RB1
negative regulation of helicase activity	1	4213.0×	0.003	TP53
cellular response to actinomycin D	1	4213.0×	0.003	TP53
regulation of intrinsic apoptotic signaling pathway by p53 class mediator	1	4213.0×	0.003	TP53
negative regulation of G1 to G0 transition	1	4213.0×	0.003	TP53
negative regulation of cell growth	2	72.0×	0.003	TP53, RB1
post-embryonic forelimb morphogenesis	1	2106.5×	0.004	ATRX
positive regulation of mitochondrial membrane permeability	1	2106.5×	0.004	TP53
positive regulation of mitotic recombination	1	2106.5×	0.004	ERCC2
oligodendrocyte apoptotic process	1	2106.5×	0.004	TP53
negative regulation of glucose catabolic process to lactate via pyruvate	1	2106.5×	0.004	TP53
negative regulation of maintenance of mitotic sister chromatid cohesion, telomeric	1	2106.5×	0.004	ATRX
negative regulation of pentose-phosphate shunt	1	2106.5×	0.004	TP53
obsolete homolactic fermentation	1	1404.3×	0.004	TP53
sister chromatid biorientation	1	1404.3×	0.004	RB1
glial cell apoptotic process	1	1404.3×	0.004	RB1

Therapeutics

Drug target analysis

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

Druggability breadth: 3 of 4 evidence-associated genes (75%) 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
TP53	NITROFURANTOIN
ERCC2	SUNITINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TP53	196	4
ERCC2	16	4
RB1	1	2
ATRX	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
NITROFURANTOIN	4	TP53
DIOSMIN	4	TP53
VERTEPORFIN	4	TP53
CANDESARTAN CILEXETIL	4	TP53
DIENESTROL	4	TP53
CLOTRIMAZOLE	4	TP53
COLCHICINE	4	TP53
NABUMETONE	4	TP53
SALMETEROL XINAFOATE	4	TP53
AMIODARONE HYDROCHLORIDE	4	TP53
FURAZOLIDONE	4	TP53
AMOXAPINE	4	TP53
RALOXIFENE HYDROCHLORIDE	4	TP53
NICARDIPINE HYDROCHLORIDE	4	TP53
SULCONAZOLE NITRATE	4	TP53
PYRITHIONE ZINC	4	TP53
LACTIC ACID	4	TP53
OXYMETHOLONE	4	TP53
CHLOROXINE	4	TP53
PROPIOLACTONE	4	TP53
CLOMIPRAMINE HYDROCHLORIDE	4	TP53
PHENYL AMINOSALICYLATE	4	TP53
THIORIDAZINE HYDROCHLORIDE	4	TP53
AMITRIPTYLINE HYDROCHLORIDE	4	TP53
ETHOPROPAZINE HYDROCHLORIDE	4	TP53
MECHLORETHAMINE HYDROCHLORIDE	4	TP53
ECONAZOLE NITRATE	4	TP53
TRIFLUPROMAZINE HYDROCHLORIDE	4	TP53
PROCHLORPERAZINE EDISYLATE	4	TP53
DEQUALINIUM CHLORIDE	4	TP53

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
TP53	869	Binding:775, ADMET:83, Functional:10, Toxicity:1
RB1	59	Binding:59
ERCC2	3	Binding:3

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ERCC2	3.6.4.12	DNA helicase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
TP53	869

Pharmacogenomics

Cohort genes with a PharmGKB record: 4; 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)
NITROFURANTOIN	4	TP53
DIOSMIN	4	TP53
VERTEPORFIN	4	TP53
CANDESARTAN CILEXETIL	4	TP53
DIENESTROL	4	TP53
CLOTRIMAZOLE	4	TP53
COLCHICINE	4	TP53
NABUMETONE	4	TP53
SALMETEROL XINAFOATE	4	TP53
AMIODARONE HYDROCHLORIDE	4	TP53
FURAZOLIDONE	4	TP53
AMOXAPINE	4	TP53
RALOXIFENE HYDROCHLORIDE	4	TP53
NICARDIPINE HYDROCHLORIDE	4	TP53
SULCONAZOLE NITRATE	4	TP53
PYRITHIONE ZINC	4	TP53
LACTIC ACID	4	TP53
OXYMETHOLONE	4	TP53
CHLOROXINE	4	TP53
PROPIOLACTONE	4	TP53
CLOMIPRAMINE HYDROCHLORIDE	4	TP53
PHENYL AMINOSALICYLATE	4	TP53
THIORIDAZINE HYDROCHLORIDE	4	TP53
AMITRIPTYLINE HYDROCHLORIDE	4	TP53
ETHOPROPAZINE HYDROCHLORIDE	4	TP53
MECHLORETHAMINE HYDROCHLORIDE	4	TP53
ECONAZOLE NITRATE	4	TP53
TRIFLUPROMAZINE HYDROCHLORIDE	4	TP53
PROCHLORPERAZINE EDISYLATE	4	TP53
DEQUALINIUM CHLORIDE	4	TP53

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	TP53, ERCC2
B	Phased (≥1) drug, not yet approved	1	RB1
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	ATRX

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
ATRX	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 323.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	112
Not specified	88
PHASE1	66
PHASE1/PHASE2	35
PHASE3	9
EARLY_PHASE1	6
PHASE2/PHASE3	5
PHASE4	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01669369	PHASE4	UNKNOWN	Clinical Trial of Lithium Carbonate Combined With Neo-adjuvant Chemotherapy to Treat Osteosarcoma
NCT04854018	PHASE4	COMPLETED	Indo-cyanine Green (ICG) in Paediatric Oncology MIS
NCT05235165	PHASE3	RECRUITING	Thoracotomy Versus Thoracoscopic Management of Pulmonary Metastases in Patients With Osteosarcoma
NCT05328258	PHASE3	RECRUITING	Use of GnRHa During Chemotherapy for Fertility Protection
NCT05691478	PHASE2/PHASE3	RECRUITING	A Study to Test the Addition of the Drug Cabozantinib to Chemotherapy in Patients With Newly Diagnosed Osteosarcoma
NCT06935409	PHASE3	ACTIVE_NOT_RECRUITING	Study of HS-20093 Versus Gemcitabine in Combination With Docetaxel in Treatment of Osteosarcoma After Previous Second-line Treatment Failure
NCT00001217	PHASE3	COMPLETED	Osteosarcoma Study #2: A Randomized Trial of Pre-Surgical Chemotherapy vs. Immediate Surgery and Adjuvant Chemotherapy in the Treatment of Non-Metastatic Osteosarcoma. A Pediatric Oncology Group Phase III Study
NCT00134030	PHASE3	COMPLETED	Combination Chemotherapy, PEG-Interferon Alfa-2b, and Surgery in Treating Patients With Osteosarcoma
NCT00180908	PHASE3	COMPLETED	Comparison of High-Dose Methotrexate (HDM) Plus Doxorubicin to HDM Plus Etoposide-Ifosfamide in Osteosarcoma Children
NCT00691236	PHASE2/PHASE3	UNKNOWN	Evaluation of Zoledronic Acid as a Single Agent or as an Adjuvant to Chemotherapy in High Grade Osteosarcoma
NCT01176981	PHASE3	COMPLETED	Outpatient Administration of High Dose Methotrexate (HD MTX) in Patients With Osteosarcoma
NCT01987596	PHASE3	TERMINATED	Study of Fixed vs. Flexible Filgrastim to Accelerate Bone Marrow Recovery After Chemotherapy in Children With Cancer
NCT02711007	PHASE2/PHASE3	COMPLETED	Apatinib for Advanced Osteosarcoma After Failure of Standard Multimodal Therapy
NCT02856048	PHASE2/PHASE3	UNKNOWN	Co-treatment With GnRH Analogs on the Ovarian Reserve in Young Women Treated With Alkylating Agents for Cancer
NCT05024253	PHASE3	COMPLETED	Perioperative Use of Tranexamic (TXA) in Bone Tumor Surgery Will Change in Blood Loss and Transfusion Requirements.
NCT05057130	PHASE2/PHASE3	UNKNOWN	Neoadjuvant Combination of Doxorubicin, Cisplatin and Methotrexate in Patients Aged 24-40 Years With Primary Bone Tumors
NCT00840047	PHASE2	ACTIVE_NOT_RECRUITING	Methionine PET/CT Studies In Patients With Cancer
NCT02243605	PHASE2	ACTIVE_NOT_RECRUITING	Cabozantinib S-malate in Treating Patients With Relapsed Osteosarcoma or Ewing Sarcoma
NCT02389244	PHASE2	ACTIVE_NOT_RECRUITING	A Phase II Study Evaluating Efficacy and Safety of Regorafenib in Patients With Metastatic Bone Sarcomas
NCT02502786	PHASE2	ACTIVE_NOT_RECRUITING	Humanized Monoclonal Antibody 3F8 (Hu3F8) With Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) in the Treatment of Recurrent Osteosarcoma
NCT02867592	PHASE2	ACTIVE_NOT_RECRUITING	Cabozantinib-S-Malate in Treating Younger Patients With Recurrent, Refractory, or Newly Diagnosed Sarcomas, Wilms Tumor, or Other Rare Tumors
NCT03155620	PHASE2	ACTIVE_NOT_RECRUITING	Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders (The Pediatric MATCH Screening Trial)
NCT03210714	PHASE2	ACTIVE_NOT_RECRUITING	Erdafitinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With FGFR Mutations (A Pediatric MATCH Treatment Trial)
NCT03213652	PHASE2	ACTIVE_NOT_RECRUITING	Ensartinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With ALK or ROS1 Genomic Alterations (A Pediatric MATCH Treatment Trial)
NCT03213704	PHASE2	ACTIVE_NOT_RECRUITING	Larotrectinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With NTRK Fusions (A Pediatric MATCH Treatment Trial)
NCT03373097	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Anti-GD2 CAR T Cells in Pediatric Patients Affected by High Risk and/or Relapsed/Refractory Neuroblastoma or Other GD2-positive Solid Tumors
NCT03449108	PHASE2	ACTIVE_NOT_RECRUITING	LN-145 or LN-145-S1 in Treating Patients With Relapsed or Refractory Ovarian Cancer, Triple Negative Breast Cancer (TNBC), Anaplastic Thyroid Cancer, Osteosarcoma, or Other Bone and Soft Tissue Sarcomas
NCT03598595	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Gemcitabine, Docetaxel, and Hydroxychloroquine in Treating Participants With Recurrent or Refractory Osteosarcoma
NCT03643133	PHASE2	ACTIVE_NOT_RECRUITING	Mifamurtide Combined With Post-operative Chemotherapy for Newly Diagnosed High Risk Osteosarcoma Patients
NCT03698994	PHASE2	ACTIVE_NOT_RECRUITING	Ulixertinib in Treating Patients With Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With MAPK Pathway Mutations (A Pediatric MATCH Treatment Trial)
NCT04040205	PHASE2	RECRUITING	Abemaciclib for Bone and Soft Tissue Sarcoma With Cyclin-Dependent Kinase (CDK) Pathway Alteration
NCT04195555	PHASE2	ACTIVE_NOT_RECRUITING	Ivosidenib in Treating Patients With Advanced Solid Tumors, Lymphoma, or Histiocytic Disorders With IDH1 Mutations (A Pediatric MATCH Treatment Trial)
NCT04284774	PHASE2	ACTIVE_NOT_RECRUITING	Tipifarnib for the Treatment of Advanced Solid Tumors, Lymphoma, or Histiocytic Disorders With HRAS Gene Alterations, a Pediatric MATCH Treatment Trial
NCT04320888	PHASE2	ACTIVE_NOT_RECRUITING	Selpercatinib for the Treatment of Advanced Solid Tumors, Lymphomas, or Histiocytic Disorders With Activating RET Gene Alterations, a Pediatric MATCH Treatment Trial
NCT04417062	PHASE2	ACTIVE_NOT_RECRUITING	Olaparib With Ceralasertib in Recurrent Osteosarcoma
NCT04668300	PHASE2	ACTIVE_NOT_RECRUITING	Oleclumab and Durvalumab for the Treatment of Recurrent, Refractory, or Metastatic Sarcoma
NCT04698785	PHASE2	RECRUITING	Efficacy of Regorafenib Combined With Best Supportive Care as Maintenance Treatment in High Grade Bone Sarcomas Patients
NCT04758000	PHASE2	RECRUITING	Metformin as Maintenance Therapy in Patients With Bone Sarcoma and High Risk of Relapse
NCT04803877	PHASE2	ACTIVE_NOT_RECRUITING	SARC038: Phase 2 Study of Regorafenib and Nivolumab in Osteosarcoma
NCT04851119	PHASE1/PHASE2	RECRUITING	Tegavivint for the Treatment of Recurrent or Refractory Solid Tumors, Including Lymphomas and Desmoid Tumors

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
MIFAMURTIDE ACID	4	13
CABOZANTINIB	4	9
DEXRAZOXANE	4	6
GLUCARPIDASE	4	4
LAROTRECTINIB	4	4
EFLORNITHINE	4	3
AZACITIDINE	4	2
DINUTUXIMAB	4	2
DOXORUBICIN	4	2
ENSARTINIB	4	2
ERDAFITINIB	4	2
IFOSFAMIDE	4	2
INDOCYANINE GREEN ACID FORM	4	2
IVOSIDENIB	4	2
SELPERCATINIB	4	2
TAZEMETOSTAT	4	2
TRILACICLIB	4	2
VEMURAFENIB	4	2
ABEMACICLIB	4	1
AFAMITRESGENE AUTOLEUCEL	4	1
AVELUMAB	4	1
CALCIUM CARBONATE	4	1
COPANLISIB	4	1
DISULFIRAM	4	1
DOSTARLIMAB	4	1
ERIBULIN MESYLATE	4	1
FERUMOXYTOL	4	1
IMATINIB MESYLATE	4	1
IMETELSTAT SODIUM	4	1
INTERFERON GAMMA-1B	4	1

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 5 predictive associations from 5 curated evidence items; also 3 oncogenic, 2 diagnostic, 1 prognostic.

Molecular subtype	Therapy	Effect	Level	CIViC
ERCC2 K751Q	Cisplatin	Resistance	CIViC B	EID676
ATRX Underexpression	VE-821 + AZ20	Sensitivity/Response	CIViC D	EID5832
RB1 Loss-of-function	Olaparib + Niraparib + Talazoparib	Sensitivity/Response	CIViC D	EID12032
ZNF217 Overexpression	Triciribine	Sensitivity/Response	CIViC D	EID12210
TP53 R273H	Doxorubicin + Methotrexate	Resistance	CIViC D	EID7430