Inflammatory myofibroblastic tumor

Summary

Inflammatory myofibroblastic tumor (MONDO:0015798) is a cancer (an umbrella term covering 5 Mondo subtypes) with 1 cohort gene (1 CIViC-evidence somatic driver) and 11 clinical trials. Molecularly, ALK Fusion confers sensitivity to Crizotinib in Inflammatory Myofibroblastic Tumor (CIViC Level A); 12 further subtype–drug associations are mapped below. Top therapeutic interventions include pazopanib, brigatinib, and crizotinib.

At a glance

• Classification: Cancer
• Umbrella term: 5 Mondo subtypes
• Cohort genes: 1
• Clinical trials: 11
• Precision-medicine evidence (CIViC): 13 subtype–drug associations

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	inflammatory myofibroblastic tumor
Mondo ID	MONDO:0015798
MeSH	D006104
Orphanet	178342
DOID	DOID:0050905
NCIT	C6481
UMLS	C0334121
MedGen	137723
GARD	0007146
MedDRA	10067917
Is cancer (heuristic)	yes

Also known as: IMT · inflammatory fibrosarcoma · inflammatory myofibroblastic neoplasm · inflammatory myofibroblastic tumor · inflammatory pseudotumor

Disease family

An umbrella term covering 5 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › connective and soft tissue neoplasm › soft tissue neoplasm › inflammatory myofibroblastic tumor

Related subtypes (17): synovium neoplasm, central nervous system mesenchymal non-meningothelial tumor, mediastinal mesenchymal tumor, nodular fasciitis, mixed endometrial stromal and smooth muscle tumor, neoplasm with perivascular epithelioid cell differentiation, desmoid tumor, congenital epulis, juvenile hyaline fibromatosis, kaposiform hemangioendothelioma, glomus tumor, Mazabraud syndrome, melanoma of soft tissue, malignant soft tissue neoplasm, soft tissue amyloid neoplasm, fibromyxoid tumor, benign soft tissue neoplasm

Subtypes (5): liver inflammatory myofibroblastic tumor, bladder inflammatory myofibroblastic tumor, lung inflammatory myofibroblastic tumor, retroperitoneal inflammatory myofibroblastic tumor, epithelioid inflammatory myofibroblastic sarcoma

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

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
ALK	Act	BRCA,HCC,NBL,NSCLC,PROSTATE,SCLC	CIViC #1

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ALK	Orphanet:146	Differentiated thyroid carcinoma
ALK	Orphanet:178342	Inflammatory myofibroblastic tumor
ALK	Orphanet:251877	Ganglioneuroblastoma
ALK	Orphanet:251992	Ganglioneuroma
ALK	Orphanet:300895	ALK-positive anaplastic large cell lymphoma
ALK	Orphanet:364043	ALK-positive large B-cell lymphoma
ALK	Orphanet:626	Large/giant congenital melanocytic nevus
ALK	Orphanet:635	Neuroblastoma

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
civic_only	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ALK	HGNC:427	ENSG00000171094	Q9UM73	ALK tyrosine kinase receptor	civic_evidence

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ALK	ALK tyrosine kinase receptor	Neuronal receptor tyrosine kinase that is essentially and transiently expressed in specific regions of the central and peripheral nervous systems and plays an important role in the genesis and differentiation of the nervous system.

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)
ALK	Kinase	yes	2.7.10.1	Prot_kinase_dom, MAM_dom, Ser-Thr/Tyr_kinase_cat_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
male germ cell	1
male germ line stem cell (sensu Vertebrata) in testis	1
sperm	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ALK	181	broad	marker	sperm, male germ cell, male germ line stem cell (sensu Vertebrata) in testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ALK	4,792

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ALK	Q9UM73	79

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 17. 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 resistance of ALK mutants	1	11420.0×	2e-04	ALK
ASP-3026-resistant ALK mutants	1	11420.0×	2e-04	ALK
NVP-TAE684-resistant ALK mutants	1	11420.0×	2e-04	ALK
alectinib-resistant ALK mutants	1	11420.0×	2e-04	ALK
brigatinib-resistant ALK mutants	1	11420.0×	2e-04	ALK
ceritinib-resistant ALK mutants	1	11420.0×	2e-04	ALK
crizotinib-resistant ALK mutants	1	11420.0×	2e-04	ALK
lorlatinib-resistant ALK mutants	1	11420.0×	2e-04	ALK
MDK and PTN in ALK signaling	1	2855.0×	7e-04	ALK
ALK mutants bind TKIs	1	951.7×	0.002	ALK
Signaling by ALK	1	571.0×	0.003	ALK
Signaling by ALK in cancer	1	271.9×	0.005	ALK
Signaling by ALK fusions and activated point mutants	1	150.3×	0.009	ALK
Diseases of signal transduction by growth factor receptors and second messengers	1	56.8×	0.021	ALK
Signaling by Receptor Tyrosine Kinases	1	51.7×	0.022	ALK
Disease	1	13.1×	0.081	ALK
Signal Transduction	1	10.2×	0.098	ALK

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
response to environmental enrichment	1	8426.0×	0.002	ALK
regulation of dopamine receptor signaling pathway	1	4213.0×	0.002	ALK
swimming behavior	1	3370.4×	0.002	ALK
response to stress	1	2407.4×	0.002	ALK
peptidyl-tyrosine autophosphorylation	1	1872.4×	0.002	ALK
phosphorylation	1	1296.3×	0.002	ALK
positive regulation of dendrite development	1	991.3×	0.003	ALK
negative regulation of lipid catabolic process	1	842.6×	0.003	ALK
regulation of neuron differentiation	1	732.7×	0.003	ALK
adult behavior	1	468.1×	0.004	ALK
energy homeostasis	1	271.8×	0.006	ALK
neuron development	1	255.3×	0.006	ALK
hippocampus development	1	230.8×	0.006	ALK
obsolete positive regulation of NF-kappaB transcription factor activity	1	205.5×	0.007	ALK
cell surface receptor protein tyrosine kinase signaling pathway	1	173.7×	0.007	ALK
protein autophosphorylation	1	145.3×	0.008	ALK
regulation of cell population proliferation	1	115.4×	0.010	ALK
regulation of apoptotic process	1	83.4×	0.013	ALK
signal transduction	1	16.1×	0.062	ALK

Therapeutics

Drugs indicated for this disease

No approved or late-stage (phase ≥3) drug is indicated for this disease; the following are in earlier-phase trials only.

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Ceritinib, Crizotinib.

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
ALK	CERITINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ALK	61	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
CERITINIB	4	ALK
BOSUTINIB	4	ALK
CRIZOTINIB	4	ALK
ALECTINIB	4	ALK
ENTRECTINIB	4	ALK
LORLATINIB	4	ALK
GILTERITINIB	4	ALK
OSIMERTINIB	4	ALK
BRIGATINIB	4	ALK
REPOTRECTINIB	4	ALK
FEDRATINIB	4	ALK
RUXOLITINIB	4	ALK
INFIGRATINIB PHOSPHATE	4	ALK
INFIGRATINIB	4	ALK
PALBOCICLIB	4	ALK
VANDETANIB	4	ALK
UPADACITINIB	4	ALK
PAZOPANIB	4	ALK
NINTEDANIB	4	ALK
SUNITINIB	4	ALK
ERLOTINIB	4	ALK
MIDOSTAURIN	4	ALK
DACTOLISIB	3	ALK
LINIFANIB	3	ALK
SEMAXANIB	3	ALK
CANERTINIB	3	ALK
ROCILETINIB	3	ALK
ALVOCIDIB	3	ALK
CEDIRANIB	3	ALK
QUERCETIN	3	ALK

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
ALK	1,815	Binding:1801, Functional:13, ADMET:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ALK	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
ALK	1,815

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

26 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)
BOSUTINIB	4	ALK
ALECTINIB	4	ALK
ENTRECTINIB	4	ALK
LORLATINIB	4	ALK
GILTERITINIB	4	ALK
OSIMERTINIB	4	ALK
REPOTRECTINIB	4	ALK
FEDRATINIB	4	ALK
RUXOLITINIB	4	ALK
INFIGRATINIB PHOSPHATE	4	ALK
INFIGRATINIB	4	ALK
PALBOCICLIB	4	ALK
VANDETANIB	4	ALK
UPADACITINIB	4	ALK
NINTEDANIB	4	ALK
SUNITINIB	4	ALK
ERLOTINIB	4	ALK
MIDOSTAURIN	4	ALK
DACTOLISIB	3	ALK
LINIFANIB	3	ALK
SEMAXANIB	3	ALK
CANERTINIB	3	ALK
ROCILETINIB	3	ALK
ALVOCIDIB	3	ALK
CEDIRANIB	3	ALK
QUERCETIN	3	ALK

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	ALK
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: 11.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	5
PHASE2/PHASE3	2
PHASE1/PHASE2	2
PHASE4	1
PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05160922	PHASE4	ACTIVE_NOT_RECRUITING	Crizotinib Continuation Clinical Study
NCT02180867	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	Radiation Therapy With or Without Combination Chemotherapy or Pazopanib Before Surgery in Treating Patients With Newly Diagnosed Non-rhabdomyosarcoma Soft Tissue Sarcomas That Can Be Removed by Surgery
NCT03874273	PHASE2/PHASE3	UNKNOWN	Study of Crizotinib in Children and Adolescents With Myofibroblastic Tumors
NCT04925609	PHASE1/PHASE2	RECRUITING	Brigatinib in Pediatric and Young Adult Patients With ALK+ ALCL, IMT or Other Solid Tumors
NCT02465528	PHASE2	TERMINATED	Ceritinib Rare Indications Study in ALK+ Tumors
NCT04260009	PHASE1/PHASE2	WITHDRAWN	Pharmacokinetics, Safety, and Efficacy of Brigatinib Monotherapy in Pediatric and Young Adult Participants With ALK+ Anaplastic Large Cell Lymphoma, Inflammatory Myofibroblastic Tumors or Other Solid Tumors
NCT07595328	Not specified	NOT_YET_RECRUITING	Warm-up of the Inspiratory Musculature and Its Impact in Swimming Performance
NCT01862146	Not specified	COMPLETED	Arterial Remodeling in Smokers
NCT02127333	Not specified	COMPLETED	Role of Oxygen for Vascular Dysfunction
NCT03085186	Not specified	NO_LONGER_AVAILABLE	Treatment With Crizotinib Single Patient Expanded Access IND 134375
NCT05540054	Not specified	COMPLETED	Inspiratory Muscle Training Efficiency Before Bronchoscopic Procedure

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
PAZOPANIB	4	3
BRIGATINIB	4	2
CRIZOTINIB	4	2
CERITINIB	4	1
IFOSFAMIDE	4	1
CHEMBL1825138	0	3
CHEMBL1825141	0	3
CHEMBL3397300	0	2
CHEMBL4068768	0	1
CHEMBL4171277	0	1

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 13 predictive associations from 17 curated evidence items; also 1 oncogenic, 1 diagnostic.

Molecular subtype	Therapy	Effect	Level	CIViC
ALK Fusion	Crizotinib	Sensitivity/Response	CIViC A	EID11122 +2
ALK Fusion	Ceritinib	Sensitivity/Response	CIViC B	EID11291 +1
ALK Fusion	Brigatinib	Sensitivity/Response	CIViC B	EID11290
TFG::ROS1 Fusion	Entrectinib	Sensitivity/Response	CIViC C	EID11860 +1
ALK Fusion	Lorlatinib	Sensitivity/Response	CIViC C	EID11294
DCTN1::ALK Fusion	Pazopanib + Crizotinib	Sensitivity/Response	CIViC C	EID10932
DCTN1::ALK Fusion	Entrectinib	Sensitivity/Response	CIViC C	EID11856
FN1::ALK Fusion	Lorlatinib	Sensitivity/Response	CIViC C	EID11292
KIF5B::ALK Fusion	Entrectinib	Sensitivity/Response	CIViC C	EID12610
RANBP2::ALK Fusion	Crizotinib	Sensitivity/Response	CIViC C	EID1244
TFG::ROS1 Fusion	Crizotinib	Sensitivity/Response	CIViC C	EID1444
TPM4::ALK Fusion	Lorlatinib	Sensitivity/Response	CIViC C	EID11293
ALK F1174L	Crizotinib	Resistance	CIViC D	EID32