Nasopharyngeal carcinoma

Summary

Nasopharyngeal carcinoma (MONDO:0015459) is a cancer with 3 cohort genes (2 CIViC-evidence somatic drivers; 52 ClinVar predisposition records) and 698 clinical trials. Molecularly, CD274 Expression confers sensitivity to Nivolumab in Nasopharynx Carcinoma (CIViC Level B). Top therapeutic interventions include toripalimab, lapatinib, and erlotinib hydrochloride.

At a glance

• Classification: Cancer
• Prevalence: 1-9 / 100 000 (Europe) [Orphanet-validated]
• Cohort genes: 3
• ClinVar variants: 52
• Clinical trials: 698
• Precision-medicine evidence (CIViC): 1 subtype–drug association

Clinical features

Epidemiology

Prevalence records

26 prevalence record(s), Orphanet, top 20 (validated / broadest geography first):

Type	Class	Value	Geography	Validation
Annual incidence	1-9 / 1 000 000	0.36	Europe	Validated
Point prevalence	1-9 / 100 000	2	Europe	Validated
Annual incidence	1-9 / 1 000 000	0.2	China	Validated
Annual incidence	1-9 / 1 000 000	0.337	Austria	Validated
Annual incidence	1-9 / 1 000 000	0.317	Belgium	Validated
Annual incidence	1-9 / 1 000 000	0.766	Bulgaria	Validated
Annual incidence	1-9 / 1 000 000	0.423	Croatia	Validated
Annual incidence	1-9 / 1 000 000	0.437	Czech Republic	Validated
Annual incidence	1-9 / 1 000 000	0.24	Estonia	Validated
Annual incidence	1-9 / 1 000 000	0.177	Finland	Validated
Annual incidence	1-9 / 1 000 000	0.35	Germany	Validated
Annual incidence	1-9 / 1 000 000	0.383	Iceland	Validated
Annual incidence	1-9 / 1 000 000	0.207	Ireland	Validated
Annual incidence	1-9 / 1 000 000	0.618	Italy	Validated
Annual incidence	1-9 / 1 000 000	0.254	Latvia	Validated
Annual incidence	1-9 / 1 000 000	0.228	Lithuania	Validated
Annual incidence	1-9 / 1 000 000	0.264	Norway	Validated
Annual incidence	1-9 / 1 000 000	0.426	Poland	Validated
Annual incidence	1-9 / 1 000 000	0.62	Portugal	Validated
Annual incidence	1-9 / 1 000 000	0.491	Slovakia	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	nasopharyngeal carcinoma
Mondo ID	MONDO:0015459
MeSH	C538339, D00007727, D000077274
Orphanet	150
DOID	DOID:9261
ICD-11	1883313543
NCIT	C3871
SNOMED CT	363398003
UMLS	C2931822
MedGen	419909
GARD	0007163
MedDRA	10028793
Anatomy (UBERON)	UBERON:0001728
Is cancer (heuristic)	yes

Also known as: cancer of nasopharynx · cancer of the nasopharynx · carcinoma of nasopharynx · carcinoma of the nasopharynx · malignant nasopharyngeal tumor · malignant nasopharyngeal tumour · malignant neoplasm of anterior wall of nasopharynx · malignant neoplasm of lateral wall of nasopharynx · malignant neoplasm of nasopharyngeal wall · malignant neoplasm of nasopharynx · malignant neoplasm of nasopharynx (disorder) [ambiguous] · malignant neoplasm of other specified sites of nasopharynx · malignant neoplasm of posterior wall of nasopharynx · malignant neoplasm of roof of nasopharynx · malignant neoplasm of superior wall of nasopharynx · malignant tumor of anterior wall of nasopharynx · malignant tumor of lateral wall of nasopharynx · malignant tumor of posterior wall of nasopharynx · malignant tumour of anterior wall of nasopharynx · malignant tumour of lateral wall of nasopharynx (+8 more)

Data availability: 52 ClinVar variants · 40 cell lines · 37 intOGen driver records.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › cancer › carcinoma › head and neck carcinoma › nasopharyngeal carcinoma

Related subtypes (15): eye carcinoma, external ear carcinoma, middle ear carcinoma, nasal cavity carcinoma, growth hormone-producing pituitary gland carcinoma, hypopharyngeal carcinoma, ameloblastic carcinoma, laryngeal small cell carcinoma, pharyngeal adenoid cystic carcinoma, head and neck squamous cell carcinoma, pituitary adenocarcinoma, carcinoma of floor of mouth, lip and oral cavity carcinoma, oropharyngeal carcinoma, nasal cavity and paranasal sinus carcinoma

Subtypes (2): carcinoma in situ of nasopharynx, undifferentiated carcinoma of nasopharynx

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

52 retrieved; paginated sample, class counts are floors:

13 conflicting classifications of pathogenicity, 13 pathogenic/likely pathogenic, 10 pathogenic, 7 uncertain significance, 3 benign, 3 likely benign, 2 benign/likely benign, 1 pathogenic/likely pathogenic/pathogenic, low penetrance

ClinVar	Variant (HGVS)	Gene	Classification	Review
12356	NM_000546.6(TP53):c.743G>A (p.Arg248Gln)	TP53	Pathogenic	reviewed by expert panel
12359	NM_000546.6(TP53):c.722C>T (p.Ser241Phe)	TP53	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
12365	NM_000546.6(TP53):c.733G>A (p.Gly245Ser)	TP53	Pathogenic	reviewed by expert panel
12366	NM_000546.6(TP53):c.818G>A (p.Arg273His)	TP53	Pathogenic	reviewed by expert panel
12368	NM_000546.6(TP53):c.839G>C (p.Arg280Thr)	TP53	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
12374	NM_000546.6(TP53):c.524G>A (p.Arg175His)	TP53	Pathogenic	reviewed by expert panel
12379	NM_000546.6(TP53):c.1010G>A (p.Arg337His)	TP53	Pathogenic/Likely pathogenic/Pathogenic, low penetrance	criteria provided, multiple submitters, no conflicts
127819	NM_000546.6(TP53):c.659A>G (p.Tyr220Cys)	TP53	Pathogenic	reviewed by expert panel
141764	NM_000546.6(TP53):c.799C>T (p.Arg267Trp)	TP53	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
141963	NM_000546.6(TP53):c.473G>A (p.Arg158His)	TP53	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
142657	NM_000546.6(TP53):c.427G>A (p.Val143Met)	TP53	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
182968	NM_000546.6(TP53):c.842A>T (p.Asp281Val)	TP53	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
182970	NM_000546.6(TP53):c.1024C>T (p.Arg342Ter)	TP53	Pathogenic	criteria provided, multiple submitters, no conflicts
231146	NM_000546.6(TP53):c.1101-1G>A	TP53	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
376615	NM_000546.6(TP53):c.641A>G (p.His214Arg)	TP53	Pathogenic	reviewed by expert panel
376625	NM_000546.6(TP53):c.395A>G (p.Lys132Arg)	TP53	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
376655	NM_000546.6(TP53):c.818G>T (p.Arg273Leu)	TP53	Pathogenic	criteria provided, multiple submitters, no conflicts
376659	NM_000546.6(TP53):c.845G>C (p.Arg282Pro)	TP53	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3892955	NC_000017.10:g.7578466_7590809del	TP53	Pathogenic	criteria provided, single submitter
428873	NM_000546.6(TP53):c.389T>C (p.Leu130Pro)	TP53	Pathogenic	criteria provided, multiple submitters, no conflicts
428908	NM_000546.6(TP53):c.559+1G>A	TP53	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
482212	NM_000546.6(TP53):c.96+1G>T	TP53	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
634674	NM_000546.6(TP53):c.298del (p.Gln100fs)	TP53	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
634682	NM_000546.6(TP53):c.817C>G (p.Arg273Gly)	TP53	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
21142	NM_000271.5(NPC1):c.709C>T (p.Pro237Ser)	NPC1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
100814	NM_000546.6(TP53):c.587G>T (p.Arg196Leu)	TP53	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1021706	NM_000546.6(TP53):c.875A>C (p.Lys292Thr)	TP53	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
127810	NM_000546.6(TP53):c.466C>T (p.Arg156Cys)	TP53	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
127818	NM_000546.6(TP53):c.604C>T (p.Arg202Cys)	TP53	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
141967	NM_000546.6(TP53):c.256G>A (p.Ala86Thr)	TP53	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 25 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
CD274	LoF	DLBCLNOS	CIViC #11335
TP53	LoF	ACC,ALL,AML,ANGS,ANSC,BCC,BL,BLADDER,BLCA,BRCA,CCRCC,CEAD,CESC,CHOL,CHRCC,CLLSLL,COAD,COADREAD,CSCC,DLBCLNOS,EGC,ES,ESCA,ESCC,GB,GBC,GBM,GIST,HCC,HGGNOS,HNSC,LGGNOS,LIPO,LMS,LNM,LUAD,LUSC,MBL,MEL,MLYM,MT,NBL,NETNOS,NHL,NPC,NSCLC,OS,OVT,PAAD,PANCREAS,PAST,PCM,PLMESO,PRAD,PRCC,PROSTATE,RCC,READ,SACA,SARCNOS,SCLC,SIC,SKCM,SKIN,SOFT_TISSUE,STAD,STOMACH,THYM,UCEC,UCS,UTUC,VULVA,WDTC,WT	CIViC #45

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TP53	Orphanet:1333	Familial pancreatic carcinoma
TP53	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
TP53	Orphanet:1501	Adrenocortical carcinoma
TP53	Orphanet:210159	Adult hepatocellular carcinoma
TP53	Orphanet:251576	Gliosarcoma
TP53	Orphanet:251579	Giant cell glioblastoma
TP53	Orphanet:251899	Choroid plexus carcinoma
TP53	Orphanet:2807	Papilloma of choroid plexus
TP53	Orphanet:293199	Pleomorphic rhabdomyosarcoma
TP53	Orphanet:3318	Essential thrombocythemia
TP53	Orphanet:524	Li-Fraumeni syndrome
TP53	Orphanet:52688	Myelodysplastic syndrome
TP53	Orphanet:585909	B-lymphoblastic leukemia/lymphoma with t(9;22)(q34.1;q11.2)
TP53	Orphanet:667662	Breast implant-associated anaplastic large cell lymphoma
TP53	Orphanet:668	Osteosarcoma
TP53	Orphanet:67038	B-cell chronic lymphocytic leukemia
TP53	Orphanet:70573	Small cell lung cancer
TP53	Orphanet:96253	Cushing disease
TP53	Orphanet:99756	Alveolar rhabdomyosarcoma
TP53	Orphanet:99757	Embryonal rhabdomyosarcoma
NPC1	Orphanet:216972	Niemann-Pick disease type C, severe perinatal form
NPC1	Orphanet:216975	Niemann-Pick disease type C, severe early infantile neurologic onset
NPC1	Orphanet:216978	Niemann-Pick disease type C, late infantile neurologic onset
NPC1	Orphanet:216981	Niemann-Pick disease type C, juvenile neurologic onset
NPC1	Orphanet:216986	Niemann-Pick disease type C, adult neurologic onset

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
civic_only	1
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CD274	HGNC:17635	ENSG00000120217	Q9NZQ7	Programmed cell death 1 ligand 1	civic_evidence
TP53	HGNC:11998	ENSG00000141510	P04637	Cellular tumor antigen p53	clinvar
NPC1	HGNC:7897	ENSG00000141458	O15118	NPC intracellular cholesterol transporter 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CD274	Programmed cell death 1 ligand 1	Plays a critical role in induction and maintenance of immune tolerance to self.
TP53	Cellular tumor antigen p53	Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence.
NPC1	NPC intracellular cholesterol transporter 1	Intracellular cholesterol transporter which acts in concert with NPC2 and plays an important role in the egress of cholesterol from the endosomal/lysosomal compartment.

Protein-family classification

Druggable: 1 · Difficult: 1 · Unknown: 1 · Druggable fraction: 0.33

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
Antibody/Immunoglobulin	1	9.7×	0.298
Transcription factor	1	2.8×	0.482
Other/Unknown	1	0.6×	0.914

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CD274	Antibody/Immunoglobulin	yes		Ig_sub, Ig-like_dom, Ig_V-set
TP53	Transcription factor	no		p53_tumour_suppressor, p53-like_TF_DNA-bd_sf, p53_tetrameristn
NPC1	Other/Unknown	no		SSD, NPC1-like, NPC1_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
cartilage tissue	1
lower lobe of lung	1
placenta	1
ganglionic eminence	1
tendon of biceps brachii	1
ventricular zone	1
adrenal tissue	1
oocyte	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CD274	208	ubiquitous	marker	cartilage tissue, placenta, lower lobe of lung
TP53	223	ubiquitous	marker	ventricular zone, ganglionic eminence, tendon of biceps brachii
NPC1	292	ubiquitous	marker	secondary oocyte, oocyte, adrenal tissue

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TP53	22,736
CD274	5,012
NPC1	2,648

Structural data

PDB: 3 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TP53	P04637	313
CD274	Q9NZQ7	76
NPC1	O15118	20

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 55. 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
Loss of function of TP53 in cancer due to loss of tetramerization ability	1	3806.7×	0.012	TP53
Regulation of TP53 Expression	1	1903.3×	0.012	TP53
Transcriptional activation of cell cycle inhibitor p21	1	951.7×	0.012	TP53
Activation of NOXA and translocation to mitochondria	1	634.4×	0.012	TP53
RUNX3 regulates CDKN1A transcription	1	543.8×	0.012	TP53
PI5P Regulates TP53 Acetylation	1	423.0×	0.012	TP53
Regulation of PD-L1(CD274) translation	1	423.0×	0.012	CD274
Activation of PUMA and translocation to mitochondria	1	380.7×	0.012	TP53
STAT3 nuclear events downstream of ALK signaling	1	346.1×	0.012	CD274
TP53 Regulates Transcription of Caspase Activators and Caspases	1	317.2×	0.012	TP53
TP53 Regulates Transcription of Death Receptors and Ligands	1	317.2×	0.012	TP53
Urea cycle	1	292.8×	0.012	TP53
Regulation of TP53 Activity through Association with Co-factors	1	271.9×	0.012	TP53
TP53 regulates transcription of several additional cell death genes whose specific roles in p53-dependent apoptosis remain uncertain	1	253.8×	0.012	TP53
Stabilization of p53	1	253.8×	0.012	TP53
TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest	1	237.9×	0.012	TP53
Formation of Senescence-Associated Heterochromatin Foci (SAHF)	1	223.9×	0.012	TP53
Zygotic genome activation (ZGA)	1	223.9×	0.012	TP53
Regulation of NF-kappa B signaling	1	211.5×	0.012	TP53
TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest	1	200.3×	0.012	TP53
SUMOylation of transcription factors	1	190.3×	0.012	TP53
TP53 Regulates Transcription of Genes Involved in Cytochrome C Release	1	181.3×	0.012	TP53
Regulation of TP53 Activity through Methylation	1	181.3×	0.012	TP53
LDL clearance	1	181.3×	0.012	NPC1
Co-inhibition by PD-1	1	173.0×	0.012	CD274
TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain	1	173.0×	0.012	TP53
PD-L1(CD274) glycosylation and translocation to plasma membrane	1	173.0×	0.012	CD274
Regulation of TP53 Activity through Acetylation	1	152.3×	0.013	TP53
Pyroptosis	1	141.0×	0.013	TP53
Oncogene Induced Senescence	1	112.0×	0.016	TP53

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
negative regulation of helicase activity	1	5617.3×	0.004	TP53
cellular response to actinomycin D	1	5617.3×	0.004	TP53
regulation of intrinsic apoptotic signaling pathway by p53 class mediator	1	5617.3×	0.004	TP53
negative regulation of G1 to G0 transition	1	5617.3×	0.004	TP53
negative regulation of tumor necrosis factor superfamily cytokine production	1	5617.3×	0.004	CD274
positive regulation of activated CD8-positive, alpha-beta T cell apoptotic process	1	5617.3×	0.004	CD274
cyclodextrin metabolic process	1	5617.3×	0.004	NPC1
positive regulation of mitochondrial membrane permeability	1	2808.7×	0.005	TP53
oligodendrocyte apoptotic process	1	2808.7×	0.005	TP53
negative regulation of glucose catabolic process to lactate via pyruvate	1	2808.7×	0.005	TP53
negative regulation of pentose-phosphate shunt	1	2808.7×	0.005	TP53
obsolete homolactic fermentation	1	1872.4×	0.005	TP53
intracellular lipid transport	1	1872.4×	0.005	NPC1
signal transduction by p53 class mediator	1	1872.4×	0.005	TP53
negative regulation of miRNA processing	1	1872.4×	0.005	TP53
intrinsic apoptotic signaling pathway in response to hypoxia	1	1872.4×	0.005	TP53
regulation of fibroblast apoptotic process	1	1872.4×	0.005	TP53
autophagy	2	73.4×	0.005	TP53, NPC1
T cell proliferation involved in immune response	1	1404.3×	0.005	TP53
positive regulation of programmed necrotic cell death	1	1404.3×	0.005	TP53
oxidative stress-induced premature senescence	1	1404.3×	0.005	TP53
negative regulation of CD8-positive, alpha-beta T cell activation	1	1404.3×	0.005	CD274
B cell lineage commitment	1	1123.5×	0.005	TP53
T cell lineage commitment	1	1123.5×	0.005	TP53
mRNA transcription	1	1123.5×	0.005	TP53
membrane raft organization	1	1123.5×	0.005	NPC1
positive regulation of RNA polymerase II transcription preinitiation complex assembly	1	1123.5×	0.005	TP53
positive regulation of thymocyte apoptotic process	1	1123.5×	0.005	TP53
cellular response to UV-C	1	1123.5×	0.005	TP53
sterol transport	1	936.2×	0.006	NPC1

Therapeutics

Drugs indicated for this disease

1 approved, 19 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Toripalimab	Approved (phase 4)
Cadonilimab	Phase 3 (in late-stage trials)
Camrelizumab	Phase 3 (in late-stage trials)
Capecitabine	Phase 3 (in late-stage trials)
Carboplatin	Phase 3 (in late-stage trials)
Celecoxib	Phase 3 (in late-stage trials)
Cetuximab	Phase 3 (in late-stage trials)
Cisplatin	Phase 3 (in late-stage trials)
Endostatin, N-Terminal-Mggshhhhh	Phase 3 (in late-stage trials)
Epirubicin	Phase 3 (in late-stage trials)
Fluorouracil	Phase 3 (in late-stage trials)
Gemcitabine	Phase 3 (in late-stage trials)
Mitomycin	Phase 3 (in late-stage trials)
Nedaplatin	Phase 3 (in late-stage trials)
Nimotuzumab	Phase 3 (in late-stage trials)
Paclitaxel	Phase 3 (in late-stage trials)
Penpulimab	Phase 3 (in late-stage trials)
Rivoceranib	Phase 3 (in late-stage trials)
Sodium Chloride	Phase 3 (in late-stage trials)
Tislelizumab	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Adebrelimab, Aspirin, Atorvastatin, Benmelstobart, Bevacizumab, Catequentinib, Dalpiciclib, Dexamethasone, Endostatin, Envafolimab, Epigalocatechin Gallate, Filgrastim, Fluzoparib, Gimeracil, Icotinib, Ipilimumab, Nivolumab, Oteracil, Oxaliplatin, Palbociclib, Pegfilgrastim, Pembrolizumab, Raltitrexed, Relatlimab, Sintilimab, Spartalizumab, Sunitinib, Surufatinib, Tegafur, Temoporfin, Withanolide D.

Drug target analysis

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

Druggability breadth: 3 of 3 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
CD274	MOCLOBEMIDE
TP53	NITROFURANTOIN
NPC1	NABUMETONE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TP53	196	4
NPC1	90	4
CD274	4	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOCLOBEMIDE	4	CD274
PYRVINIUM	4	CD274
RIFABUTIN	4	CD274
NITROFURANTOIN	4	TP53
DIOSMIN	4	TP53
VERTEPORFIN	4	TP53
CANDESARTAN CILEXETIL	4	TP53
DIENESTROL	4	TP53
CLOTRIMAZOLE	4	TP53
COLCHICINE	4	TP53
NABUMETONE	4	NPC1, TP53
SALMETEROL XINAFOATE	4	TP53
AMIODARONE HYDROCHLORIDE	4	TP53
FURAZOLIDONE	4	TP53
AMOXAPINE	4	TP53
RALOXIFENE HYDROCHLORIDE	4	TP53
NICARDIPINE HYDROCHLORIDE	4	TP53
SULCONAZOLE NITRATE	4	TP53
PYRITHIONE ZINC	4	TP53
LACTIC ACID	4	TP53
OXYMETHOLONE	4	TP53
CHLOROXINE	4	TP53
PROPIOLACTONE	4	TP53
CLOMIPRAMINE HYDROCHLORIDE	4	TP53
PHENYL AMINOSALICYLATE	4	TP53
THIORIDAZINE HYDROCHLORIDE	4	TP53
AMITRIPTYLINE HYDROCHLORIDE	4	TP53
ETHOPROPAZINE HYDROCHLORIDE	4	TP53
MECHLORETHAMINE HYDROCHLORIDE	4	TP53
ECONAZOLE NITRATE	4	TP53

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
TP53	869	Binding:775, ADMET:83, Functional:10, Toxicity:1
CD274	525	Binding:520, Functional:5
NPC1	18	Binding:13, Functional:5

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
CD274	525
TP53	869

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

30 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)
MOCLOBEMIDE	4	CD274
PYRVINIUM	4	CD274
RIFABUTIN	4	CD274
NITROFURANTOIN	4	TP53
DIOSMIN	4	TP53
VERTEPORFIN	4	TP53
CANDESARTAN CILEXETIL	4	TP53
DIENESTROL	4	TP53
CLOTRIMAZOLE	4	TP53
COLCHICINE	4	TP53
NABUMETONE	4	NPC1, TP53
SALMETEROL XINAFOATE	4	TP53
AMIODARONE HYDROCHLORIDE	4	TP53
FURAZOLIDONE	4	TP53
AMOXAPINE	4	TP53
RALOXIFENE HYDROCHLORIDE	4	TP53
NICARDIPINE HYDROCHLORIDE	4	TP53
SULCONAZOLE NITRATE	4	TP53
PYRITHIONE ZINC	4	TP53
LACTIC ACID	4	TP53
OXYMETHOLONE	4	TP53
CHLOROXINE	4	TP53
PROPIOLACTONE	4	TP53
CLOMIPRAMINE HYDROCHLORIDE	4	TP53
PHENYL AMINOSALICYLATE	4	TP53
THIORIDAZINE HYDROCHLORIDE	4	TP53
AMITRIPTYLINE HYDROCHLORIDE	4	TP53
ETHOPROPAZINE HYDROCHLORIDE	4	TP53
MECHLORETHAMINE HYDROCHLORIDE	4	TP53
ECONAZOLE NITRATE	4	TP53

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	3	CD274, TP53, NPC1
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: 698.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	254
Not specified	183
PHASE3	132
PHASE1	64
PHASE1/PHASE2	41
PHASE2/PHASE3	11
EARLY_PHASE1	8
PHASE4	5

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06457503	PHASE4	RECRUITING	A Study of Toripalimab in Combination With Cisplatin and Gemcitabine in Participants With Recurrent Metastatic Nasopharyngeal Cancer
NCT01344356	PHASE4	COMPLETED	Stereotactic Body Radiotherapy for Head and Neck Tumors
NCT02293356	PHASE4	UNKNOWN	Phase IV Clinical Trial of Nimotuzumab in the Treatment of Nasopharyngeal Carcinoma
NCT02948699	PHASE4	UNKNOWN	A Research About Nutrition Impact for Local Advanced Nasopharyngeal Carcinoma Patients
NCT04292990	PHASE4	UNKNOWN	Comparison of Transdermal Fentanyl and Morphine for Oral Mucositis Pain in Nasopharyngeal Cancer Patients
NCT02135042	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	Individualized Treatment Treating Patients With Stage II-IVB Nasopharyngeal Cancer Based on EBV DNA
NCT02460887	PHASE3	ACTIVE_NOT_RECRUITING	The Role of Induction Gemcitabine and Cisplatin in Locoregionally Advanced Nasopharyngeal Carcinoma in the Era of IMRT
NCT03306121	PHASE3	ACTIVE_NOT_RECRUITING	TPF+CCRT vs.CCRT+PF in High Risk Nasopharyngeal Carcinoma
NCT03503136	PHASE3	NOT_YET_RECRUITING	Nedaplatin Versus Cisplatin and Capecitabine Versus Fluorouracil in IC + CCRT for Locoregionally Advanced NPC
NCT03529279	PHASE3	NOT_YET_RECRUITING	CNG Staging Compared With 8th UICC of NPC for Treatment Decision-marking and Selection of Chemotherapy and Radiotherapy
NCT03840421	PHASE3	ACTIVE_NOT_RECRUITING	GP Vs PF As Induction Chemotherapy Combined with CCRT for Locoregionally Advanced Nasopharyngeal Carcinoma
NCT03907826	PHASE3	RECRUITING	PD-1 Antibody Combined With Chemoradiotherapy in Recurrent Nasopharyngeal Carcinoma Patients
NCT03919552	PHASE3	RECRUITING	Cisplatin-based and Carboplatin-based Chemoradiation in Locoregionally Advanced Nasopharyngeal Carcinoma
NCT04136886	PHASE3	RECRUITING	Concurrent Chemotherapy for Recurrent T3/T4 Nasopharyngeal Carcinoma
NCT04215510	PHASE3	NOT_YET_RECRUITING	Early Recurrent Nasopharyngeal Cancer: the Effect of Surgery vs IMRT
NCT04376866	PHASE3	RECRUITING	Toripalimab for Local-regional Recurrent Nasopharyngeal Carcinoma
NCT04384627	PHASE3	ACTIVE_NOT_RECRUITING	Reducing Target Volumes in NPC Treated With Induction Chemotherapy Followed by Concurrent Chemoradiotherapy
NCT04436965	PHASE3	RECRUITING	Effect of Standard Nutrition Therapy on Nutritional Status and Prognosis in Locoregionally Advanced Nasopharyngeal Carcinoma Patients With Malnutrition
NCT04437329	PHASE3	RECRUITING	Nedaplatin Versus Cisplatin in Treatment for Nasopharyngeal Carcinoma
NCT04448522	PHASE3	RECRUITING	Reduced vs Conventional Dosage Intensity-modulated Radiotherapy for Chemotherapy-sensitive Stage II-III Nasopharyngeal Carcinoma
NCT04453813	PHASE3	RECRUITING	Toripalimab Plus Concurrent Chemo-radiotherapy for Unresectable Locally Recurrent Nasopharyngeal Carcinoma
NCT04453826	PHASE3	RECRUITING	Concurrent and Adjuvant PD1 Treatment Combined With Chemo-radiotherapy for High-risk Nasopharyngeal Carcinoma
NCT04456322	PHASE3	ACTIVE_NOT_RECRUITING	Radiotherapy Plus Nimotuzumab or Cisplatin in Nasopharyngeal Carcinoma
NCT04778956	PHASE3	RECRUITING	Toripalimab Plus Surgery vs Surgery Alone for Resectable Recurrent Nasopharyngeal Carcinoma
NCT04890522	PHASE2/PHASE3	NOT_YET_RECRUITING	An Open-label, Multicentre, Phase II/III RCT of PFLL Versus GP Combined With JS001 as the First-line Therapy for mNPC
NCT04907370	PHASE3	ACTIVE_NOT_RECRUITING	PD-1 Blockade Combined With De-intensified Chemoradiotherapy Sparing Concurrent Cisplatin in Nasopharyngeal Carcinoma
NCT04944914	PHASE3	RECRUITING	Camrelizumab Plus Stereotactic Body Radiotherapy vs Camrelizumab Alone For Oligometastatic Nasopharyngeal Carcinoma
NCT04974398	PHASE3	ACTIVE_NOT_RECRUITING	A Study of Penpulimab (AK105) in the First-line Treatment of Recurrent or Metastatic Nasopharyngeal Carcinoma
NCT05062005	PHASE3	RECRUITING	ICCRT vs. CRT for Locally Advanced Nasopharyngeal Carcinoma
NCT05063552	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	Testing the Use of Investigational Drugs Atezolizumab and/or Bevacizumab With or Without Standard Chemotherapy in the Second-Line Treatment of Advanced-Stage Head and Neck Cancers
NCT05145660	PHASE3	ACTIVE_NOT_RECRUITING	Optimization of Cervical Nodal CTV for Early and Medium Stage NPC
NCT05211232	PHASE3	ACTIVE_NOT_RECRUITING	Neoadjuvant and Adjuvant Tislelizumab for Nasopharyngeal Carcinoma
NCT05294172	PHASE3	ACTIVE_NOT_RECRUITING	KL-A167 Injection Combined With Cisplatin and Gemcitabine vs Placebo Combined With Cisplatin and Gemcitabine in the Treatment of Recurrent or Metastatic Nasopharyngeal Carcinoma
NCT05304468	PHASE3	ACTIVE_NOT_RECRUITING	Reduced-dose Versus Standard Dose Radiotherapy for Nasopharyngeal Carcinomain
NCT05340491	PHASE3	RECRUITING	Chemoradiotherapy Plus Anti-PD1 in Recurrent NPC: A Multicenter, Open-label, Randomised, Controlled, Phase III Trial
NCT05342792	PHASE3	RECRUITING	Metronomic Capecitabine With or Without PD-1 Antibody as Adjuvant Therapy in High-risk Nasopharyngeal Carcinoma
NCT05433597	PHASE2/PHASE3	NOT_YET_RECRUITING	A Two-blinded, Multicentre, Phase II/III RCT of Concurrent Chemo-radiotherapy Combined or Not Combined With TNF as the Therapy for LA-NPC
NCT05527470	PHASE3	RECRUITING	Induction Chemotherapy Followed by IMRT or Concurrent Chemoradiotherapy in Locoregionally Advanced Nasopharyngeal Carcinoma
NCT05587374	PHASE3	ACTIVE_NOT_RECRUITING	Cadonilimab (PD-1/CTLA-4 Bispecific Blockade) and Chemoradiotherapy in Nasopharyngeal Carcinoma (GEMSTONE)
NCT05674305	PHASE3	RECRUITING	Radiotherapy Alone Versus Concurrent Chemo-radiotherapy for Nasopharyngeal Carcincoma Patients With Undectable EBV DNA After One Cylce Neoadjuvant Chemotherpy

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
TORIPALIMAB	4	10
LAPATINIB	4	6
ERLOTINIB HYDROCHLORIDE	4	5
SORAFENIB	4	5
FOSAPREPITANT	4	3
TROPISETRON	4	3
CETUXIMAB	4	2
GEMCITABINE	4	2
TABELECLEUCEL	4	2
TISLELIZUMAB	4	2
VALGANCICLOVIR	4	2
VALPROIC ACID	4	2
VORINOSTAT	4	2
ATEZOLIZUMAB	4	1
AVELUMAB	4	1
BETA CAROTENE	4	1
BORTEZOMIB D-MANNITOL	4	1
CABOZANTINIB S-MALATE	4	1
CAPECITABINE	4	1
CARBOPLATIN	4	1
CISPLATIN	4	1
DASATINIB	4	1
DASATINIB ANHYDROUS	4	1
EDARAVONE	4	1
ETOPOSIDE PHOSPHATE	4	1
FLOXURIDINE	4	1
FLUCICLOVINE F18	4	1
IFOSFAMIDE	4	1
INFIGRATINIB	4	1
INTERFERON BETA-1A	4	1

Precision-medicine subtype map (CIViC)

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

Molecular subtype	Therapy	Effect	Level	CIViC
CD274 Expression	Nivolumab	Sensitivity/Response	CIViC B	EID9010