Tumor of salivary gland

Summary

Tumor of salivary gland (MONDO:0021357) is a cancer with 1 cohort gene (1 CIViC-evidence somatic driver; 1 ClinVar predisposition record) and 23 clinical trials. Top therapeutic interventions include alectinib, apalutamide, and gonadorelin acetate.

At a glance

• Classification: Cancer
• Cohort genes: 1
• ClinVar variants: 1
• Clinical trials: 23

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	tumor of salivary gland
Mondo ID	MONDO:0021357
EFO	EFO:1000384
NCIT	C3361
SNOMED CT	235132004
UMLS	C0036095
MedGen	20641
Anatomy (UBERON)	UBERON:0001044
Is cancer (heuristic)	yes

Also known as: neoplasm of saliva-secreting gland · neoplasm of salivary gland · neoplasm of the salivary gland · saliva-secreting gland neoplasm · saliva-secreting gland neoplasm (disease) · saliva-secreting gland tumor · saliva-secreting gland tumour · salivary gland neoplasm · salivary gland tumor · salivary gland tumour · tumor of saliva-secreting gland · tumor of the salivary gland · tumour of saliva-secreting gland · tumour of the salivary gland

Data availability: 1 ClinVar variant.

Disease family

An umbrella term covering 4 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › mouth disorder › salivary gland disorder › tumor of salivary gland

Related subtypes (8): submandibular gland disorder, benign lymphoepithelial lesion of salivary gland, mucocele of salivary gland, parotid disorder, necrotizing sialometaplasia, sialadenitis, sialolithiasis, Sjogren syndrome

Subtypes (4): salivary gland cancer, neoplasm of major salivary gland, neoplasm of minor salivary gland, benign neoplasm of salivary gland

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 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
160364	NM_005343.4(HRAS):c.182A>G (p.Gln61Arg)	HRAS	Likely pathogenic	criteria provided, multiple submitters, no conflicts

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
HRAS	Act	ANGS,BLCA,BRCA,COADREAD,CSCC,HNSC,LUSC,NPC,PGNG,PRAD,PROSTATE,THYM,UTUC,WDTC	CIViC #2747

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
HRAS	Orphanet:146	Differentiated thyroid carcinoma
HRAS	Orphanet:2612	Linear nevus sebaceus syndrome
HRAS	Orphanet:2874	Phakomatosis pigmentokeratotica
HRAS	Orphanet:3071	Costello syndrome
HRAS	Orphanet:79414	Woolly hair nevus

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
HRAS	HGNC:5173	ENSG00000174775	P01112	GTPase HRas	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
HRAS	GTPase HRas	Involved in the activation of Ras protein signal transduction.

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
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
HRAS	Enzyme (other)	yes	3.6.5.2	Small_GTPase, Small_GTP-bd, Small_GTPase_Ras-type

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
skin of abdomen	1
skin of leg	1
zone of skin	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
HRAS	139	ubiquitous	marker	skin of abdomen, skin of leg, zone of skin

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
HRAS	8,064

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
HRAS	P01112	246

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 68. 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
Signaling by RAS GAP mutants	1	3806.7×	0.003	HRAS
Signaling by RAS GTPase mutants	1	3806.7×	0.003	HRAS
Activation of RAS in B cells	1	2284.0×	0.003	HRAS
RAS signaling downstream of NF1 loss-of-function variants	1	1631.4×	0.003	HRAS
Estrogen-stimulated signaling through PRKCZ	1	1631.4×	0.003	HRAS
SOS-mediated signalling	1	1427.5×	0.003	HRAS
Activated NTRK3 signals through RAS	1	1268.9×	0.003	HRAS
EGFR Transactivation by Gastrin	1	1142.0×	0.003	HRAS
SHC-related events triggered by IGF1R	1	1142.0×	0.003	HRAS
Activated NTRK2 signals through RAS	1	1142.0×	0.003	HRAS
MET activates RAS signaling	1	1038.2×	0.003	HRAS
Signaling by FGFR4 in disease	1	951.7×	0.003	HRAS
Activated NTRK2 signals through FRS2 and FRS3	1	951.7×	0.003	HRAS
Constitutive Signaling by Overexpressed ERBB2	1	951.7×	0.003	HRAS
p38MAPK events	1	878.5×	0.003	HRAS
Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants	1	878.5×	0.003	HRAS
Signaling by PDGFRA extracellular domain mutants	1	878.5×	0.003	HRAS
PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases	1	815.7×	0.003	HRAS
GRB2 events in EGFR signaling	1	761.3×	0.003	HRAS
Erythropoietin activates RAS	1	761.3×	0.003	HRAS
Signaling by FLT3 ITD and TKD mutants	1	761.3×	0.003	HRAS
SHC1 events in ERBB4 signaling	1	713.8×	0.003	HRAS
SHC1 events in EGFR signaling	1	713.8×	0.003	HRAS
Constitutive Signaling by EGFRvIII	1	713.8×	0.003	HRAS
Signalling to RAS	1	671.8×	0.003	HRAS
Insulin receptor signalling cascade	1	671.8×	0.003	HRAS
Signaling by ERBB2 ECD mutants	1	671.8×	0.003	HRAS
GRB2 events in ERBB2 signaling	1	634.4×	0.003	HRAS
Tie2 Signaling	1	601.0×	0.003	HRAS
SHC-mediated cascade:FGFR3	1	601.0×	0.003	HRAS

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 miRNA metabolic process	1	5617.3×	0.007	HRAS
oncogene-induced cell senescence	1	2407.4×	0.007	HRAS
T-helper 1 type immune response	1	1872.4×	0.007	HRAS
Schwann cell development	1	1053.2×	0.007	HRAS
regulation of long-term neuronal synaptic plasticity	1	991.3×	0.007	HRAS
positive regulation of ruffle assembly	1	991.3×	0.007	HRAS
regulation of neurotransmitter receptor localization to postsynaptic specialization membrane	1	887.0×	0.007	HRAS
defense response to protozoan	1	601.9×	0.007	HRAS
cellular response to gamma radiation	1	601.9×	0.007	HRAS
positive regulation of protein targeting to membrane	1	561.7×	0.007	HRAS
positive regulation of wound healing	1	526.6×	0.007	HRAS
adipose tissue development	1	401.2×	0.008	HRAS
fibroblast proliferation	1	391.9×	0.008	HRAS
intrinsic apoptotic signaling pathway	1	358.6×	0.008	HRAS
positive regulation of fibroblast proliferation	1	295.6×	0.009	HRAS
cellular senescence	1	295.6×	0.009	HRAS
myelination	1	251.5×	0.009	HRAS
positive regulation of epithelial cell proliferation	1	244.2×	0.009	HRAS
positive regulation of type II interferon production	1	224.7×	0.009	HRAS
insulin receptor signaling pathway	1	221.7×	0.009	HRAS
Ras protein signal transduction	1	205.5×	0.010	HRAS
animal organ morphogenesis	1	191.5×	0.010	HRAS
neuron apoptotic process	1	185.2×	0.010	HRAS
positive regulation of JNK cascade	1	163.6×	0.010	HRAS
regulation of actin cytoskeleton organization	1	157.5×	0.010	HRAS
MAPK cascade	1	153.2×	0.010	HRAS
T cell receptor signaling pathway	1	151.8×	0.010	HRAS
chemotaxis	1	135.9×	0.011	HRAS
regulation of cell population proliferation	1	115.4×	0.013	HRAS
negative regulation of neuron apoptotic process	1	110.9×	0.013	HRAS

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): Rezvilutamide.

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
HRAS	LONAFARNIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
HRAS	4	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
LONAFARNIB	4	HRAS
STALLIMYCIN	2	HRAS
L-778123 FREE BASE	1	HRAS
BMS-214662	1	HRAS

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
HRAS	48	Binding:45, Functional:3

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
HRAS	3.6.5.2	small monomeric GTPase

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

4 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)
LONAFARNIB	4	HRAS
STALLIMYCIN	2	HRAS
L-778123 FREE BASE	1	HRAS
BMS-214662	1	HRAS

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	HRAS
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: 23.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	11
PHASE2	7
PHASE1	3
PHASE2/PHASE3	1
PHASE1/PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05786716	PHASE2/PHASE3	RECRUITING	DETERMINE Trial Treatment Arm 04: Trastuzumab in Combination With Pertuzumab in Adult, Paediatric and Teenage/Young Adult Patients With Cancers With HER2 Amplification or Activating Mutations
NCT04325828	PHASE2	ACTIVE_NOT_RECRUITING	A Study of Apalutamide Combined With GnRH Agonist in Participants With Androgen Receptor Positive Salivary Gland Carcinoma
NCT04825938	PHASE2	NOT_YET_RECRUITING	Neoadjuvant Toripalimab in Combination With Carboplatin and Nab-paclitaxel in Untreated Salivary Gland Malignant Neoplasms
NCT05000892	PHASE2	RECRUITING	Neoadjuvant Sintilimab in Combination With Carboplatin and Nab-paclitaxel in Untreated Salivary Gland Malignant Neoplasms
NCT02776163	PHASE2	COMPLETED	Postoperative Concurrent Chemoradiotherapy in Treating Patients With High-Risk Salivary Gland Carcinomas
NCT03602079	PHASE1/PHASE2	COMPLETED	Study of A166 in Patients With Relapsed/Refractory Cancers Expressing HER2 Antigen or Having Amplified HER2 Gene
NCT04644315	PHASE2	TERMINATED	A Home-Based Approach Study to Evaluate the Efficacy and Safety of Alectinib in Locally-Advanced or Metastatic ALK-Positive Solid Tumors
NCT04832438	PHASE2	WITHDRAWN	9-ING-41 Plus Carboplatin in Patients With Advanced, Metastatic Salivary Gland Carcinoma
NCT05601401	PHASE2	UNKNOWN	Phase II Study of RC48-ADC in Treating Patients With Salivary Gland Tumors Expressing HER2
NCT04969835	PHASE1	RECRUITING	A Study Evaluating the Safety, Pharmacokinetics and Early Efficacy of AVA6000 in Solid Tumours
NCT02921984	PHASE1	COMPLETED	Concurrent Chemotherapy Based on Genetic Testing in Patients With High-Risk Salivary Gland Tumors
NCT04249947	PHASE1	TERMINATED	P-PSMA-101 CAR-T Cells in the Treatment of Subjects With Metastatic Castration-Resistant Prostate Cancer (mCRPC) and Advanced Salivary Gland Cancers (SGC)
NCT04452162	Not specified	RECRUITING	Physiologic MR Imaging of Salivary Gland Tumors
NCT06047236	Not specified	RECRUITING	Immune Biomarker Study for Salivary Gland Carcinoma
NCT06356272	Not specified	RECRUITING	Oropharynx (OPX) Biomarker Trial
NCT07072143	Not specified	RECRUITING	An International Study on Pediatric Patients With Rare Tumors.
NCT00568438	Not specified	COMPLETED	Immunohistochemical & Immunoblot Analysis of NIS (Na+/I-Symporter) in Archival & Frozen Tissue Sample
NCT03942380	Not specified	UNKNOWN	Cell-free Tumor DNA in Head and Neck Cancer Patients
NCT04970875	Not specified	COMPLETED	Partial Modified Blair Incision on Benign Tumor Parotidectomy Scar’s Characteristics
NCT05087706	Not specified	UNKNOWN	Exploratory Study of Molecular Profile-Associated Evidence Guided Precision Therapy for Salivary Gland Cancer（MAPS）
NCT05390294	Not specified	COMPLETED	Survival With Patients Treated With Salivary Gland Cancer
NCT05581979	Not specified	COMPLETED	PSMA-PET Imaging of Salivary Gland Tumours and Other Rare Cancers
NCT06034782	Not specified	COMPLETED	Diagnostic Accuracy of Fine Needle Aspiration in Patients With Salivary Gland Tumors.

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
ALECTINIB	4	1
APALUTAMIDE	4	1
GONADORELIN ACETATE	4	1
PERTUZUMAB	4	1
TRASTUZUMAB	4	1
NEDAPLATIN	3	1
ELRAGLUSIB	2	1
GLYCOLIC ACID	2	1
RIMIDUCID	2	1
TRASTUZUMAB BOTIDOTIN	2	1
ZENIDOLOL	2	1
AVA-6000	1	1
CHEMBL2370644	0	1
CHEMBL4878843	0	1