Salivary gland adenoid cystic carcinoma

Summary

Salivary gland adenoid cystic carcinoma (MONDO:0003175) is a cancer with 1 cohort gene (1 CIViC-evidence somatic driver) and 7 clinical trials. Molecularly, IGF1R Overexpression confers sensitivity to Crizotinib + Gefitinib + Linsitinib in Salivary Gland Adenoid Cystic Carcinoma (CIViC Level D). Top therapeutic interventions include lapatinib, dasatinib anhydrous, and bortezomib.

At a glance

• Classification: Cancer
• Cohort genes: 1
• Clinical trials: 7
• Precision-medicine evidence (CIViC): 1 subtype–drug association

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	salivary gland adenoid cystic carcinoma
Mondo ID	MONDO:0003175
DOID	DOID:4866
NCIT	C8026
SNOMED CT	422833009
UMLS	C0279751
MedGen	79034
GARD	0023398
Anatomy (UBERON)	UBERON:0001044
Is cancer (heuristic)	yes

Also known as: adenoid cystic cancer · adenoid cystic carcinoma (morphologic abnormality) · adenoid cystic carcinoma of salivary gland · adenoid cystic carcinoma of the salivary gland · cylindroma (morphologic abnormality) · saliva-secreting gland adenoid cystic carcinoma · salivary gland adenoid cystic cancer · salivary gland adenoid cystic carcinoma

Data availability: 15 cell lines.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › digestive system disorder › digestive system cancer › oral cavity cancer › salivary gland cancer › salivary gland carcinoma › salivary gland adenoid cystic carcinoma

Related subtypes (12): major salivary gland carcinoma, salivary gland basal cell adenocarcinoma, salivary gland carcinoma ex pleomorphic adenoma, salivary gland large cell carcinoma, salivary gland small cell carcinoma, salivary gland epithelial myoepithelial carcinoma, salivary gland mucoepidermoid carcinoma, salivary gland squamous cell carcinoma, salivary duct carcinoma, minor salivary gland carcinoma, salivary gland mucinous adenocarcinoma, mammary analog secretory carcinoma

Subtypes (2): major salivary gland adenoid cystic carcinoma, minor salivary gland adenoid cystic carcinoma

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

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
IGF1R			CIViC #2899

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
IGF1R	Orphanet:73273	Growth delay due to insulin-like growth factor I resistance

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
IGF1R	HGNC:5465	ENSG00000140443	P08069	Insulin-like growth factor 1 receptor	civic_evidence

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
IGF1R	Insulin-like growth factor 1 receptor	Receptor tyrosine kinase which mediates actions of insulin-like growth factor 1 (IGF1).

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)
IGF1R	Kinase	yes	2.7.10.1	Rcpt_L-dom, Prot_kinase_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
adrenal tissue	1
caput epididymis	1
corpus epididymis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
IGF1R	285	ubiquitous	marker	caput epididymis, corpus epididymis, adrenal tissue

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
IGF1R	6,823

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
IGF1R	P08069	46

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. 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
SHC-related events triggered by IGF1R	1	1142.0×	0.002	IGF1R
IRS-related events triggered by IGF1R	1	1038.2×	0.002	IGF1R
Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R)	1	951.7×	0.002	IGF1R
Respiratory syncytial virus (RSV) attachment and entry	1	496.5×	0.003	IGF1R
Extra-nuclear estrogen signaling	1	170.4×	0.006	IGF1R

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
positive regulation of protein-containing complex disassembly	1	4213.0×	0.004	IGF1R
peptidyl-tyrosine autophosphorylation	1	1872.4×	0.004	IGF1R
transcytosis	1	1685.2×	0.004	IGF1R
dendritic spine maintenance	1	1296.3×	0.004	IGF1R
amyloid-beta clearance	1	936.2×	0.004	IGF1R
regulation of JNK cascade	1	887.0×	0.004	IGF1R
insulin-like growth factor receptor signaling pathway	1	495.6×	0.006	IGF1R
cellular response to amyloid-beta	1	391.9×	0.007	IGF1R
negative regulation of MAPK cascade	1	300.9×	0.008	IGF1R
cellular response to glucose stimulus	1	267.5×	0.008	IGF1R
insulin receptor signaling pathway	1	221.7×	0.008	IGF1R
phosphatidylinositol 3-kinase/protein kinase B signal transduction	1	210.7×	0.008	IGF1R
positive regulation of cold-induced thermogenesis	1	163.6×	0.010	IGF1R
protein autophosphorylation	1	145.3×	0.010	IGF1R
positive regulation of MAPK cascade	1	80.6×	0.017	IGF1R
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1	78.4×	0.017	IGF1R
positive regulation of cell migration	1	61.7×	0.020	IGF1R
immune response	1	47.1×	0.025	IGF1R
negative regulation of apoptotic process	1	34.8×	0.031	IGF1R
positive regulation of cell population proliferation	1	33.6×	0.031	IGF1R
signal transduction	1	16.1×	0.062	IGF1R

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
IGF1R	FEDRATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
IGF1R	27	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
FEDRATINIB	4	IGF1R
ENTRECTINIB	4	IGF1R
CERITINIB	4	IGF1R
BRIGATINIB	4	IGF1R
PAZOPANIB	4	IGF1R
NINTEDANIB	4	IGF1R
SUNITINIB	4	IGF1R
CRIZOTINIB	4	IGF1R
LINSITINIB	3	IGF1R
QUERCETIN	3	IGF1R
LESTAURTINIB	3	IGF1R
FORETINIB	2	IGF1R
CENISERTIB	2	IGF1R
ILORASERTIB	2	IGF1R
R-406	2	IGF1R
TOZASERTIB	2	IGF1R
BMS-754807	2	IGF1R
ELLAGIC ACID	2	IGF1R
PF-00562271	1	IGF1R
KW-2449	1	IGF1R
XL-228	1	IGF1R
ASP-3026	1	IGF1R
NT-219	1	IGF1R
CONTELTINIB	1	IGF1R
PF-03814735	1	IGF1R
PD-0166285	1	IGF1R
AEW-541	1	IGF1R

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
IGF1R	1,091	Binding:1037, Functional:53, ADMET:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
IGF1R	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
IGF1R	1,091

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

27 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)
FEDRATINIB	4	IGF1R
ENTRECTINIB	4	IGF1R
CERITINIB	4	IGF1R
BRIGATINIB	4	IGF1R
PAZOPANIB	4	IGF1R
NINTEDANIB	4	IGF1R
SUNITINIB	4	IGF1R
CRIZOTINIB	4	IGF1R
LINSITINIB	3	IGF1R
QUERCETIN	3	IGF1R
LESTAURTINIB	3	IGF1R
FORETINIB	2	IGF1R
CENISERTIB	2	IGF1R
ILORASERTIB	2	IGF1R
R-406	2	IGF1R
TOZASERTIB	2	IGF1R
BMS-754807	2	IGF1R
ELLAGIC ACID	2	IGF1R
PF-00562271	1	IGF1R
KW-2449	1	IGF1R
XL-228	1	IGF1R
ASP-3026	1	IGF1R
NT-219	1	IGF1R
CONTELTINIB	1	IGF1R
PF-03814735	1	IGF1R
PD-0166285	1	IGF1R
AEW-541	1	IGF1R

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	IGF1R
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: 7.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	5
EARLY_PHASE1	1
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00077428	PHASE2	COMPLETED	Bortezomib Followed by the Addition of Doxorubicin at Disease Progression in Treating Patients With Locally Advanced, Recurrent, or Metastatic Adenoid Cystic Carcinoma (Cancer) of the Head and Neck
NCT00095563	PHASE2	COMPLETED	Lapatinib in Treating Patients With Recurrent and/or Metastatic Adenoid Cystic Cancer or Other Salivary Gland Cancers
NCT00859937	PHASE2	COMPLETED	Dasatinib in Treating Patients With Recurrent or Metastatic Malignant Salivary Gland Tumors
NCT01175980	PHASE2	COMPLETED	Vorinostat in Treating Patients With Locally Advanced, Recurrent, or Metastatic Adenoid Cystic Carcinoma
NCT01604772	PHASE2	COMPLETED	Akt Inhibitor MK2206 in Treating Patients With Progressive, Recurrent, or Metastatic Adenoid Cyst Carcinoma
NCT05553782	EARLY_PHASE1	RECRUITING	Drug Screening Using Novel IMD in Salivary and Head and Neck Cancers
NCT07507578	Not specified	RECRUITING	A Multi-omics Approach to Disclose Progression and Underlying Biology of Head and Neck Adenoid Cystic Carcinoma

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
LAPATINIB	4	3
DASATINIB ANHYDROUS	4	2
BORTEZOMIB	4	1
VORINOSTAT	4	1
CHEMBL4583196	0	1

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 1 predictive associations from 1 curated evidence items.

Molecular subtype	Therapy	Effect	Level	CIViC
IGF1R Overexpression	Crizotinib + Gefitinib + Linsitinib	Sensitivity/Response	CIViC D	EID9024