Adenoid cystic carcinoma

Summary

Adenoid cystic carcinoma (MONDO:0004971) is a cancer (an umbrella term covering 17 Mondo subtypes) with 3 cohort genes (2 CIViC-evidence somatic drivers; 5 ClinVar predisposition records) and 59 clinical trials. Top therapeutic interventions include axitinib, bortezomib, and enfortumab vedotin.

At a glance

• Classification: Cancer
• Umbrella term: 17 Mondo subtypes
• Cohort genes: 3
• ClinVar variants: 5
• Clinical trials: 59

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	adenoid cystic carcinoma
Mondo ID	MONDO:0004971
EFO	EFO:0000231
MeSH	D003528
DOID	DOID:0080202
ICD-11	2127202862
NCIT	C2970
UMLS	C0010606
MedGen	41382
GARD	0005743
Is cancer (heuristic)	yes

Also known as: adenocystic carcinoma · adenoid cystic cancer · adenoid cystic carcinoma · cribriform carcinoma · cylindroid adenocarcinoma · cylindroma

Data availability: 5 ClinVar variants · 12 intOGen driver records.

Disease family

An umbrella term covering 17 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › cancer › carcinoma › adenocarcinoma › adenoid cystic carcinoma

Related subtypes (63): epididymal adenocarcinoma, rete testis adenocarcinoma, seminal vesicle adenocarcinoma, ethmoid sinus adenocarcinoma, lacrimal gland adenocarcinoma, papillary adenocarcinoma, fallopian tube adenocarcinoma, bladder adenocarcinoma, ovarian adenocarcinoma, trabecular adenocarcinoma, middle ear adenocarcinoma, bile duct adenocarcinoma, granular cell carcinoma, small intestine adenocarcinoma, urethra adenocarcinoma, villous adenocarcinoma, thymus gland adenocarcinoma, nasal cavity adenocarcinoma, ureter adenocarcinoma, adenocarcinoma in situ, gastroesophageal junction adenocarcinoma, maxillary sinus adenocarcinoma, mucinous adenocarcinoma, acinar cell carcinoma, breast adenocarcinoma, clear cell adenocarcinoma, colorectal adenocarcinoma, endometrioid adenocarcinoma, esophageal adenocarcinoma, gastric adenocarcinoma, lung adenocarcinoma, prostate adenocarcinoma, renal cell carcinoma, signet ring cell carcinoma, cervical adenocarcinoma, serous adenocarcinoma, endometrium adenocarcinoma, sweat gland carcinoma, cystadenocarcinoma, tubular adenocarcinoma, mesonephric adenocarcinoma, scirrhous adenocarcinoma, pancreatic adenocarcinoma, follicular variant thyroid gland papillary carcinoma, gallbladder adenocarcinoma, hepatoid adenocarcinoma, intestinal type adenocarcinoma, micropapillary serous carcinoma, minor salivary gland adenocarcinoma, poorly differentiated thyroid gland carcinoma, salivary gland basal cell adenocarcinoma, submandibular gland adenocarcinoma, sebaceous adenocarcinoma, hepatocellular carcinoma, parathyroid gland carcinoma, pituitary adenocarcinoma, vaginal adenocarcinoma, Paget disease, diffuse type adenocarcinoma, vulvar adenocarcinoma, thyroid gland adenocarcinoma, gastroesophageal adenocarcinoma, adenoacanthoma

Subtypes (17): lymph node adenoid cystic carcinoma, salivary gland adenoid cystic carcinoma, prostate adenoid cystic carcinoma, cutaneous adenocystic carcinoma, lung adenoid cystic carcinoma, adenoid cystic breast carcinoma, esophageal adenoid cystic carcinoma, Bartholin gland adenoid cystic carcinoma, cervical adenoid cystic carcinoma, lacrimal gland adenoid cystic carcinoma, laryngeal adenoid cystic carcinoma, paranasal sinus adenoid cystic carcinoma, pharyngeal adenoid cystic carcinoma, tracheal adenoid cystic carcinoma, vaginal adenoid cystic carcinoma, adenoid cystic carcinoma of the corpus uteri, adenoid cystic carcinoma of oropharynx

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

5 retrieved; paginated sample, class counts are floors:

5 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
495137	t(6;9)(q23.3;p22.3)	MYB	Pathogenic	no assertion criteria provided
495139	t(6;9)(q23.3;p22.3)	MYB	Pathogenic	no assertion criteria provided
495140	t(6;9)(q23.3;p22.3)	MYB	Pathogenic	no assertion criteria provided
495136	t(8;9)(q13.1;p22.3)	MYBL1	Pathogenic	no assertion criteria provided
495138	t(6;9)(q23.3;p22.3)	NFIB	Pathogenic	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 5 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
MYB			CIViC #3730
MYBL1			CIViC #3731

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MYB	Orphanet:251671	Angiocentric glioma
MYB	Orphanet:86849	Acute basophilic leukemia
MYB	Orphanet:99861	Precursor T-cell acute lymphoblastic leukemia
NFIB	Orphanet:714407	Developmental delay-macrocephaly-corpus callosum dysgenesis-intellectual disability syndrome due to NFIB mutation
NFIB	Orphanet:714413	9p23p22.2 microdeletion syndrome

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
MYB	HGNC:7545	ENSG00000118513	P10242	Transcriptional activator Myb	clinvar
MYBL1	HGNC:7547	ENSG00000185697	P10243	Myb-related protein A	clinvar
NFIB	HGNC:7785	ENSG00000147862	O00712	Nuclear factor 1 B-type	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MYB	Transcriptional activator Myb	Transcriptional activator; DNA-binding protein that specifically recognize the sequence 5’-YAAC[GT]G-3'.
MYBL1	Myb-related protein A	Transcription factor that specifically recognizes the sequence 5’-YAAC[GT]G-3'.
NFIB	Nuclear factor 1 B-type	Transcriptional activator of GFAP, essential for proper brain development.

Protein-family classification

Druggable: 0 · Difficult: 2 · 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
Transcription factor	2	5.5×	0.081
Other/Unknown	1	0.6×	0.914

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MYB	Transcription factor	no		SANT/Myb, Homeodomain-like_sf, Tscrpt_reg_Wos2-domain
MYBL1	Transcription factor	no		SANT/Myb, Homeodomain-like_sf, Tscrpt_reg_Wos2-domain
NFIB	Other/Unknown	no		CTF/NFI, MAD_homology1_Dwarfin-type, CTF/NFI_DNA-bd_N

Expression context

Cohort genes with no expression data: 0.

3 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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
bronchial epithelial cell	1
epithelium of bronchus	1
mucosa of sigmoid colon	1
calcaneal tendon	1
sperm	1
vena cava	1
epithelium of mammary gland	1
mammary duct	1
pericardium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MYB	183	broad	marker	mucosa of sigmoid colon, bronchial epithelial cell, epithelium of bronchus
MYBL1	257	ubiquitous	marker	calcaneal tendon, vena cava, sperm
NFIB	292	ubiquitous	marker	pericardium, epithelium of mammary gland, mammary duct

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MYB	3,155
NFIB	2,496
MYBL1	2,087

Intra-cohort edges

A	B	Sources
MYBL1	NFIB	string_interaction

Structural data

PDB: 1 · AlphaFold-only: 2 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
NFIB	O00712	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
MYB	P10242	59.16
MYBL1	P10243	58.19

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 19. Enrichment computed across 3 evidence-associated genes (3 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 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Specification of the neural plate border	1	211.5×	0.031	MYB
RNA Polymerase III Transcription Termination	1	165.5×	0.031	NFIB
PIWI-interacting RNA (piRNA) biogenesis	1	131.3×	0.031	MYBL1
Gene Silencing by RNA	1	119.0×	0.031	MYBL1
RNA Polymerase III Abortive And Retractive Initiation	1	92.8×	0.031	NFIB
Gastrulation	1	86.5×	0.031	MYB
Gene expression (Transcription)	2	11.9×	0.031	MYB, MYBL1
Transcriptional regulation by RUNX1	1	48.8×	0.045	MYB
ESR-mediated signaling	1	42.8×	0.045	MYB
Transcriptional regulation of granulopoiesis	1	41.8×	0.045	MYB
Signaling by Nuclear Receptors	1	34.0×	0.049	MYB
RUNX1 regulates transcription of genes involved in differentiation of HSCs	1	31.7×	0.049	MYB
Estrogen-dependent gene expression	1	25.2×	0.057	MYB
Factors involved in megakaryocyte development and platelet production	1	22.1×	0.060	MYB
Hemostasis	1	12.0×	0.103	MYB
RNA Polymerase II Transcription	1	7.5×	0.151	MYB
Generic Transcription Pathway	1	5.0×	0.204	MYB
Developmental Biology	1	4.8×	0.204	MYB
Signal Transduction	1	3.4×	0.267	MYB

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regeneration	1	5617.3×	0.002	NFIB
lung ciliated cell differentiation	1	5617.3×	0.002	NFIB
positive regulation of piRNA transcription	1	5617.3×	0.002	MYBL1
negative regulation of epithelial cell proliferation involved in lung morphogenesis	1	5617.3×	0.002	NFIB
mitotic cell cycle	2	89.2×	0.002	MYB, MYBL1
positive regulation of DNA-templated transcription	3	27.9×	0.002	MYB, MYBL1, NFIB
cell differentiation involved in salivary gland development	1	2808.7×	0.003	NFIB
negative regulation of mesenchymal cell proliferation involved in lung development	1	2808.7×	0.003	NFIB
positive regulation of transcription by RNA polymerase II	3	14.9×	0.003	MYB, MYBL1, NFIB
principal sensory nucleus of trigeminal nerve development	1	1872.4×	0.003	NFIB
positive regulation of hepatic stellate cell proliferation	1	1872.4×	0.003	MYB
positive regulation of testosterone secretion	1	1872.4×	0.003	MYB
glial cell fate specification	1	1404.3×	0.003	NFIB
myeloid cell development	1	1404.3×	0.003	MYB
negative regulation of hematopoietic progenitor cell differentiation	1	1404.3×	0.003	MYB
skeletal muscle cell proliferation	1	1123.5×	0.004	MYB
club cell differentiation	1	1123.5×	0.004	NFIB
salivary gland cavitation	1	1123.5×	0.004	NFIB
positive regulation of hepatic stellate cell activation	1	936.2×	0.004	MYB
anterior commissure morphogenesis	1	802.5×	0.005	NFIB
glandular epithelial cell differentiation	1	702.2×	0.005	NFIB
type II pneumocyte differentiation	1	702.2×	0.005	NFIB
positive regulation of transforming growth factor beta production	1	702.2×	0.005	MYB
stem cell division	1	624.1×	0.005	MYB
T-helper 2 cell differentiation	1	624.1×	0.005	MYB
type I pneumocyte differentiation	1	510.7×	0.005	NFIB
cell proliferation in forebrain	1	432.1×	0.006	NFIB
hindbrain development	1	374.5×	0.007	NFIB
negative regulation of DNA binding	1	374.5×	0.007	NFIB
exit from mitosis	1	351.1×	0.007	NFIB

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): Avelumab, Axitinib, Bortezomib, Dasatinib Anhydrous, Dovitinib, Doxorubicin, Everolimus, Lenvatinib, Pembrolizumab, Regorafenib, Rivoceranib, Tretinoin, Tucidinostat.

Drug target analysis

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

Druggability breadth: 1 of 3 evidence-associated genes (33%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MYB	0	0
MYBL1	0	0
NFIB	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
MYB	7	Binding:7

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; 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	3	MYB, MYBL1, NFIB

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
MYB	7	—
MYBL1	0	—
NFIB	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 59.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	35
Not specified	9
PHASE1	8
PHASE1/PHASE2	6
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02780310	PHASE2	ACTIVE_NOT_RECRUITING	Testing Lenvatinib in Patients With Adenoid Cystic Carcinoma
NCT02834013	PHASE2	ACTIVE_NOT_RECRUITING	Nivolumab and Ipilimumab in Treating Patients With Rare Tumors
NCT03556228	PHASE1/PHASE2	RECRUITING	VMD-928 Monotherapy and in Combination With Pembrolizumab to Treat TrkA Overexpression Driven Solid Tumors or Lymphoma
NCT04140526	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Safety, PK and Efficacy of ONC-392 in Monotherapy and in Combination of Anti-PD-1 in Advanced Solid Tumors and NSCLC
NCT04209660	PHASE2	ACTIVE_NOT_RECRUITING	Lenvatinib and Pembrolizumab in People With Advanced Adenoid Cystic Carcinoma and Other Salivary Gland Cancers
NCT04214366	PHASE2	RECRUITING	Adenoid Cystic Carcinoma and Carbon Ion Only Irradiation
NCT04895735	PHASE2	ACTIVE_NOT_RECRUITING	MC200708 Pemetrexed and Pembrolizumab for the Treatment of Recurrent and/or Metastatic Salivary Gland Cancer
NCT05010629	PHASE2	ACTIVE_NOT_RECRUITING	9-ING-41 Plus Carboplatin in Salivary Gland Carcinoma
NCT05774899	PHASE1/PHASE2	RECRUITING	CB-103 With Either Lenvatinib or Abemaciclib in Patients With NOTCH ACC
NCT06118086	PHASE1/PHASE2	RECRUITING	Study of REM-422 in Patients With Recurrent, Metastatic, or Unresectable Adenoid Cystic Carcinoma
NCT06638931	PHASE2	RECRUITING	Agnostic Therapy in Rare Solid Tumors
NCT06781567	PHASE2	RECRUITING	Clinical Trial of HG146 Administered to Participants with Adenoid Cystic Carcinoma
NCT06805617	PHASE2	RECRUITING	A Phase 2 Trial of Ivonescimab for Patients With Advanced, Metastatic Salivary Gland Cancers
NCT06891560	PHASE2	RECRUITING	A Study of Enfortumab Vedotin in People With Adenoid Cystic Carcinoma
NCT07162480	PHASE2	RECRUITING	Phase II Trial of Puxitatug Samrotecan (AZD8205) in Advanced, Recurrent or Metastatic (R/M) Aggressive Adenoid Cystic Carcinoma Subtype I (ACC-I)
NCT07320508	PHASE2	RECRUITING	Epirubicin Interventional Chemotherapy for Sinonasal Adenoid Cystic Carcinoma (SNACC): A Prospective Study
NCT07521670	PHASE2	NOT_YET_RECRUITING	Sacituzumab Tirumotecan in Recurrent/Metastatic Adenoid Cystic Carcinoma and Papillary Thyroid Carcinoma (STRAP)
NCT07522879	PHASE2	RECRUITING	A Study of Becotatug Vedotin (MRG003) Combined With Epirubicin as Neoadjuvant Therapy for EGFR-Positive, Unresectable Recurrent Sinonasal Adenoid Cystic Carcinoma
NCT00581360	PHASE2	COMPLETED	Phase II Trial of Doxorubicin and Bortezomib in Patients With Incurable Adenoid Cystic Carcinoma of the Head and Neck
NCT00886132	PHASE2	COMPLETED	A Study of Sunitinib in Recurrent and/or Metastatic Adenoid Cystic Carcinoma of the Salivary Glands
NCT01152840	PHASE2	COMPLETED	Study of RAD001 in Adenoid Cystic Carcinoma
NCT01192087	PHASE1/PHASE2	UNKNOWN	Adenoid Cystic Carcinoma, Erbitux, and Particle Therapy
NCT01417143	PHASE2	COMPLETED	Dovitinib in Adenoid Cystic Carcinoma
NCT01524692	PHASE2	COMPLETED	Study of Dovitinib (TKI258) in Adenoid Cystic Carcinoma
NCT01558661	PHASE2	COMPLETED	Axitinib (AG-013736) in Patients With Progressive, Recurrent/Metastatic Adenoid Cystic Carcinoma
NCT02098538	PHASE2	COMPLETED	Regorafenib in Patients With Progressive, Recurrent/Metastatic Adenoid Cystic Carcinoma
NCT02775370	PHASE2	UNKNOWN	A Study of Apatinib in Recurrent/Metastatic Adenoid Cystic Carcinoma of the Head and Neck
NCT02883374	PHASE2	UNKNOWN	Chidamide for Advanced Cephalic and Cervical Adenocystic Carcinoma: Evaluation of Efficiency and Safety
NCT02942693	PHASE2	UNKNOWN	Trail Evaluating Particle Therapy With or Without Apatinib for H&N Adenoid Cystic Carcinoma
NCT03087019	PHASE2	COMPLETED	Pembrolizumab With or Without Radiation in Patients With Recurrent or Metastatic Adenoid Cystic Carcinoma
NCT03422679	PHASE1/PHASE2	TERMINATED	Study of CB-103 in Adult Patients With Advanced or Metastatic Solid Tumours and Haematological Malignancies
NCT03639168	PHASE2	COMPLETED	Chidamide Combined With Cisplatin in Head and Neck Adenoid Cystic Carcinoma (HNACC)
NCT03691207	PHASE2	COMPLETED	A Study Of AL101In Patients With Adenoid Cystic Carcinoma (ACC) Bearing Activating Notch Mutations
NCT03990571	PHASE2	COMPLETED	Axitinib and Avelumab in Treating Patients With Recurrent or Metastatic Adenoid Cystic Carcinoma
NCT03999684	PHASE2	COMPLETED	A Trial of All-trans Retinoic Acid (ATRA) in Advanced Adenoid Cystic Carcinoma
NCT04119453	PHASE2	TERMINATED	A Study to Evaluate the Efficacy and Safety of Rivoceranib in Participants With Recurrent or Metastatic Adenoid Cystic Carcinoma (ACC)
NCT04291300	PHASE2	COMPLETED	Lutetium-177-PSMA Radioligand Therapy in Advanced Salivary Gland Cancer Patients
NCT04832438	PHASE2	WITHDRAWN	9-ING-41 Plus Carboplatin in Patients With Advanced, Metastatic Salivary Gland Carcinoma
NCT06199453	PHASE2	WITHDRAWN	The Evaluation of the Effectiveness, Safety and Tolerability of Treatment, Using a PSMA-Lu177, in Patients with ACC- an Open, Non-commercial Clinical Trial
NCT06322576	PHASE2	TERMINATED	177Lu-PSMA (177Lu-PNT2002) in PSMA-Positive Adenoid Cystic Carcinoma

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
AXITINIB	4	2
BORTEZOMIB	4	1
ENFORTUMAB VEDOTIN	4	1
GALLIUM GA 68 GOZETOTIDE	4	1
LENVATINIB	4	1
LUTETIUM LU-177 VIPIVOTIDE TETRAXETAN	4	1
REGORAFENIB	4	1
TRETINOIN	4	1
RIVOCERANIB	3	4
BECOTATUG VEDOTIN	3	1
DOVITINIB	3	1
IVONESCIMAB	3	1
SACITUZUMAB TIRUMOTECAN	3	1
TUCIDINOSTAT	3	1
ELRAGLUSIB	2	2
LIMANTRAFIN	2	2
OSUGACESTAT	2	2
BRONTICTUZUMAB	2	1
FAPI GA-68	2	1
FELMETATUG VEDOTIN	2	1
LUTETIUM LU 177 ZADAVOTIDE GURAXETAN	2	1
ONC-392	2	1
RIMIDUCID	2	1
CHEMBL275117	0	1
CHEMBL4517714	0	1
CHEMBL5405436	0	1
CHEMBL4578973	0	1
CHEMBL4087968	0	1
CHEMBL3939307	0	1