Desmoplastic small round cell tumor

Summary

Desmoplastic small round cell tumor (MONDO:0019373) is a cancer with 1 cohort gene and 30 clinical trials. Top therapeutic interventions include ifosfamide, lurbinectedin, and pasireotide.

At a glance

• Classification: Cancer
• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 1
• Phenotypes (HPO): 18
• Clinical trials: 30

Clinical features

Epidemiology

Prevalence records

3 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		300	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated
Annual incidence	<1 / 1 000 000		Europe	Validated

Signs & symptoms

Clinical features (HPO)

18 HPO clinical features (Orphanet curated; top 18 by frequency):

HPO ID	Term	Frequency
HP:0002027	Abdominal pain	Very frequent (80-99%)
HP:0002585	Abnormality of the peritoneum	Very frequent (80-99%)
HP:0002716	Lymphadenopathy	Very frequent (80-99%)
HP:0003270	Abdominal distention	Very frequent (80-99%)
HP:0100242	Sarcoma	Very frequent (80-99%)
HP:0001824	Weight loss	Frequent (30-79%)
HP:0002017	Nausea and vomiting	Frequent (30-79%)
HP:0002240	Hepatomegaly	Frequent (30-79%)
HP:0002595	Ileus	Frequent (30-79%)
HP:0100721	Mediastinal lymphadenopathy	Frequent (30-79%)
HP:0001541	Ascites	Occasional (5-29%)
HP:0001903	Anemia	Occasional (5-29%)
HP:0002894	Neoplasm of the pancreas	Occasional (5-29%)
HP:0004326	Cachexia	Occasional (5-29%)
HP:0010788	Testicular neoplasm	Occasional (5-29%)
HP:0100006	Neoplasm of the central nervous system	Occasional (5-29%)
HP:0100526	Neoplasm of the lung	Occasional (5-29%)
HP:0100615	Ovarian neoplasm	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	desmoplastic small round cell tumor
Mondo ID	MONDO:0019373
EFO	EFO:1000895
MeSH	D058405
Orphanet	83469
DOID	DOID:6785
NCIT	C8300
UMLS	C0281508
MedGen	83833
GARD	0006265
MedDRA	10064581, 10064587
Is cancer (heuristic)	yes

Also known as: Desmoplas. small round cell tumor · Desmoplas. small round cell tumour · Desmoplastic small round cell tumor · desmoplastic small round cell tumor · Desmoplastic small round cell tumour · Desmoplastic small round-cell neoplasm · Desmoplastic small round-cell tumor · Desmoplastic small round-cell tumour · desmoplastic small-round-cell tumor · desmoplastic small-round-cell tumour · DSRCT · Polyphenotypic small round cell tumor · Polyphenotypic small round cell tumour

Data availability: 1 ClinVar variant · 6 cell lines.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › cancer › sarcoma › small cell sarcoma › desmoplastic small round cell tumor

Related subtypes (5): small cell osteogenic sarcoma, mesenchymal chondrosarcoma, EWSR1-negative small round cell tumor, sarcoma with BCOR genetic alterations, round cell sarcoma with EWSR1-non-ETS fusion

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

1 retrieved; paginated sample, class counts are floors:

1 other

ClinVar	Variant (HGVS)	Gene	Classification	Review
438792	NM_001192.3(TNFRSF17):c.524C>T (p.Thr175Met)	NPIPB2	other	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

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

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
NPIPB2	HGNC:37451	ENSG00000234719	A6NJ64	Nuclear pore complex-interacting protein family member B2	clinvar

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
NPIPB2	Other/Unknown	no		NPIP, NPIP_N

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
cerebellar vermis	1
quadriceps femoris	1
thymus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
NPIPB2	138	ubiquitous	marker	cerebellar vermis, thymus, quadriceps femoris

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NPIPB2	447

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
NPIPB2	A6NJ64	56.54

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
NPIPB2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

0 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.

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
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	1	NPIPB2

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)
NPIPB2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 30.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	10
PHASE1/PHASE2	7
PHASE1	7
Not specified	4
EARLY_PHASE1	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01946529	PHASE2	ACTIVE_NOT_RECRUITING	Therapeutic Trial for Patients With Ewing Sarcoma Family of Tumor and Desmoplastic Small Round Cell Tumors
NCT04022213	PHASE2	ACTIVE_NOT_RECRUITING	A Study of the Drug I131-Omburtamab in People With Desmoplastic Small Round Cell Tumors and Other Solid Tumors in the Peritoneum
NCT05918640	PHASE1/PHASE2	RECRUITING	Lurbinectedin in FET-Fused Tumors
NCT06277154	PHASE2	RECRUITING	MASCT-I Combined With Doxorubicin and Ifosfamide for First-line Treatment of Advanced Soft Tissue Sarcoma
NCT06456359	PHASE2	RECRUITING	Pasireotide as Maintenance Treatment in Synovial Sarcoma and Desmoplastic Small Round Cell Tumor
NCT06625190	PHASE1/PHASE2	RECRUITING	Alpha/Beta T and B Cell Depletion With Zoledronic Acid for Solid Tumors
NCT06709495	PHASE1/PHASE2	RECRUITING	Phase 1/2 Trial to Evaluate the Safety and Efficacy of PEEL-224 in Combination With Vincristine and Temozolomide in Adolescents and Young Adults With Relapsed or Refractory Sarcomas
NCT06836505	PHASE1/PHASE2	RECRUITING	Safety and Efficacy of CAR-T Cell Therapy for Relapsed/refractory Neuroblastoma and Desmoplastic Small Round Cell Tumors: a Single-arm, Open-label Trial.
NCT06849986	PHASE2	RECRUITING	IO Combined With AI as First-line Treatment for Patients With Soft Tissue Sarcoma(TAIS)
NCT07328425	PHASE2	RECRUITING	Clinical Study in Adult and Young Adult Patients With Advanced Desmoplastic Small Round Cell Tumor (DSRCT) ISG-TULIPS
NCT00563680	PHASE2	COMPLETED	QUILT-3.025: A Phase 2 Study of AMG 479 in Relapsed or Refractory Ewing’s Family Tumor and Desmoplastic Small Round Cell Tumors
NCT01125449	PHASE2	WITHDRAWN	Study of High Dose Intravenous (IV) Ascorbic Acid in Measurable Solid Tumor Disease
NCT02982486	PHASE2	UNKNOWN	A Phase II of Nivolumab Plus Ipilimumab in Non-resectable Sarcoma and Endometrial Carcinoma
NCT04095221	PHASE1/PHASE2	COMPLETED	A Study of the Drugs Prexasertib, Irinotecan, and Temozolomide in People With Desmoplastic Small Round Cell Tumor and Rhabdomyosarcoma
NCT04145349	PHASE1/PHASE2	COMPLETED	CAMPFIRE: A Study of Ramucirumab (LY3009806) in Children and Young Adults With Desmoplastic Small Round Cell Tumor
NCT04530487	PHASE2	TERMINATED	Donor Stem Cell Transplant After Chemotherapy for the Treatment of Recurrent or Refractory High-Risk Solid Tumors in Pediatric and Adolescent-Young Adults
NCT05266196	PHASE1/PHASE2	UNKNOWN	A Rollover Protocol to Allow for Continued Access to the LSD1 Inhibitor Seclidemstat (SP-2577)
NCT03618381	PHASE1	ACTIVE_NOT_RECRUITING	EGFR806 CAR T Cell Immunotherapy for Recurrent/Refractory Solid Tumors in Children and Young Adults
NCT04483778	PHASE1	ACTIVE_NOT_RECRUITING	B7H3 CAR T Cell Immunotherapy for Recurrent/Refractory Solid Tumors in Children and Young Adults
NCT04897321	PHASE1	RECRUITING	B7-H3-Specific Chimeric Antigen Receptor Autologous T-Cell Therapy for Pediatric Patients With Solid Tumors (3CAR)
NCT00436657	PHASE1	COMPLETED	Continuous Hyperthermic Peritoneal Perfusion (CHPP) With Cisplatin for Children With Peritoneal Cancer
NCT02982941	PHASE1	COMPLETED	Enoblituzumab (MGA271) in Children With B7-H3-expressing Solid Tumors
NCT03600649	PHASE1	UNKNOWN	Clinical Trial of SP-2577 (Seclidemstat) in Patients With Relapsed or Refractory Ewing or Ewing-related Sarcomas
NCT04901806	PHASE1	TERMINATED	Study of PBI-200 in Subjects With NTRK-Fusion-Positive Solid Tumors
NCT01189643	EARLY_PHASE1	ACTIVE_NOT_RECRUITING	Irinotecan, Temozolomide and Bevacizumab in Combination With Existing High Dose Alkylator Based Chemotherapy for Treatment of Newly Diagnosed Patients With Desmoplastic Small Round Cell Tumor
NCT04213794	EARLY_PHASE1	TERMINATED	Heated Intra-peritoneal Chemotherapy With Doxorubicin and Cisplatin for Abdominal for Pelvic Tumors in Pediatric Patients
NCT03967834	Not specified	RECRUITING	Multimodal Immune Characterization of RAre Soft Tissue Sarcoma - MIRAS Project From SARRA (SARcome RAre) Project of the French Sarcoma Group
NCT04690374	Not specified	RECRUITING	Registry to Collect Health Information About Desmoplastic Small Round Cell Tumor
NCT02834169	Not specified	UNKNOWN	French National Registry of Rare Peritoneal Surface Malignancies
NCT03874455	Not specified	NO_LONGER_AVAILABLE	Tazemetostat Expanded Access Program for Adults With Solid Tumors

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
IFOSFAMIDE	4	3
LURBINECTEDIN	4	2
PASIREOTIDE	4	2
RAMUCIRUMAB	4	1
SODIUM THIOSULFATE	4	1
TAZEMETOSTAT	4	1
SECLIDEMSTAT	2	2
ENOBLITUZUMAB	2	1
PALTIMATRECTINIB	2	1
PREXASERTIB	2	1
CHEMBL5397028	0	2
CHEMBL3753202	0	1
CHEMBL5398431	0	1