Skin squamous cell carcinoma

Summary

Skin squamous cell carcinoma (MONDO:0002529) is a cancer (an umbrella term covering 9 Mondo subtypes) with 5 cohort genes (5 CIViC-evidence somatic drivers) and 166 clinical trials. The dominant Reactome pathway is EGFR Transactivation by Gastrin (3 cohort genes). Molecularly, EGFR P753S confers sensitivity to Cetuximab + Sirolimus in Skin Squamous Cell Carcinoma (CIViC Level C); 9 further subtype–drug associations are mapped below. Top therapeutic interventions include cemiplimab, dacomitinib anhydrous, and cosibelimab.

At a glance

• Classification: Cancer
• Umbrella term: 9 Mondo subtypes
• Cohort genes: 5
• Clinical trials: 166
• Precision-medicine evidence (CIViC): 10 subtype–drug associations

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	skin squamous cell carcinoma
Mondo ID	MONDO:0002529
DOID	DOID:3151
ICD-11	1448983042
NCIT	C4819
SNOMED CT	254651007
UMLS	C0553723
MedGen	107512
Anatomy (UBERON)	UBERON:0000014
Is cancer (heuristic)	yes

Also known as: CSCC · cutaneous squamous cell carcinoma · epidermoid carcinoma of skin · epidermoid carcinoma of the skin · epidermoid skin carcinoma · skin squamous cell cancer · skin squamous cell carcinoma · squamous cell carcinoma - skin · squamous cell carcinoma of skin · squamous cell carcinoma of the skin · squamous cell skin carcinoma · zone of skin squamous cell carcinoma

Data availability: 131 cell lines · 22 intOGen driver records.

Disease family

An umbrella term covering 9 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › integumentary system disorder › integumentary system cancer › skin cancer › skin carcinoma › skin squamous cell carcinoma

Related subtypes (12): labia minora carcinoma, labia majora carcinoma, cutaneous Paget disease, anal margin carcinoma, cutaneous mucoepidermoid carcinoma, eyelid carcinoma, Borst-Jadassohn intraepidermal carcinoma, skin carcinoma in situ, skin basal cell carcinoma, vulvar seborrheic keratosis, skin appendage carcinoma, cutaneous neuroendocrine carcinoma

Subtypes (9): anal margin squamous cell carcinoma, plantar verrucous skin carcinoma, sarcomatoid squamous cell skin carcinoma, skin basaloid carcinoma, acantholytic squamous cell skin carcinoma, pseudovascular skin squamous cell carcinoma, clear cell squamous cell skin carcinoma, skin squamous cell carcinoma in situ, skin adenosquamous 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: 39 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
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
KMT2C	LoF	ACC,ACYC,AML,ANSC,BCC,BLCA,BRCA,CCRCC,CEAD,CESC,CHOL,COAD,COADREAD,ES,ESCA,GBC,HCC,HNSC,LUAD,LUSC,MBL,MEL,NPC,OVT,PAAD,PANCREAS,PANET,PAST,PGNG,PRAD,PRCC,PROSTATE,RCC,SACA,SCLC,STAD,STOMACH,UCEC,WDTC	CIViC #14089
EGFR	Act	BRCA,COADREAD,GB,GBM,HGGNOS,LGGNOS,LUAD,LUSC,NSCLC,PAST,PCM,READ,SIC	CIViC #19
HRAS	Act	ANGS,BLCA,BRCA,COADREAD,CSCC,HNSC,LUSC,NPC,PGNG,PRAD,PROSTATE,THYM,UTUC,WDTC	CIViC #2747
KRAS	Act	ALL,AML,ANSC,BLADDER,BLCA,BRCA,CEAD,CESC,CHOL,CLLSLL,COAD,COADREAD,DLBCLNOS,EGC,ESCA,ESCC,HCC,LUAD,LUSC,MEL,MGCT,MT,NSCLC,OVT,PAAD,PANCREAS,PAST,PCM,PRAD,PRCC,READ,STAD,STOMACH,UCEC,UCS,WDTC	CIViC #30

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
KMT2C	Orphanet:261652	Kleefstra syndrome due to a point mutation
EGFR	Orphanet:251576	Gliosarcoma
EGFR	Orphanet:251579	Giant cell glioblastoma
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
KRAS	Orphanet:1333	Familial pancreatic carcinoma
KRAS	Orphanet:1340	Cardiofaciocutaneous syndrome
KRAS	Orphanet:144	Lynch syndrome
KRAS	Orphanet:146	Differentiated thyroid carcinoma
KRAS	Orphanet:2396	Encephalocraniocutaneous lipomatosis
KRAS	Orphanet:251615	Pilomyxoid astrocytoma
KRAS	Orphanet:2612	Linear nevus sebaceus syndrome
KRAS	Orphanet:268114	RAS-associated autoimmune leukoproliferative disease
KRAS	Orphanet:3339	Oculoectodermal syndrome
KRAS	Orphanet:648	Noonan syndrome
KRAS	Orphanet:86834	Juvenile myelomonocytic leukemia

Cohort genes → proteins

5 cohort genes, 5 distinct canonical proteins.

Evidence partition

Subset	Genes
civic_only	5

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TP53	HGNC:11998	ENSG00000141510	P04637	Cellular tumor antigen p53	civic_evidence
KMT2C	HGNC:13726	ENSG00000055609	Q8NEZ4	Histone-lysine N-methyltransferase 2C	civic_evidence
EGFR	HGNC:3236	ENSG00000146648	P00533	Epidermal growth factor receptor	civic_evidence
HRAS	HGNC:5173	ENSG00000174775	P01112	GTPase HRas	civic_evidence
KRAS	HGNC:6407	ENSG00000133703	P01116	GTPase KRas	civic_evidence

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TP53	Cellular tumor antigen p53	Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence.
KMT2C	Histone-lysine N-methyltransferase 2C	Histone methyltransferase that catalyzes methyl group transfer from S-adenosyl-L-methionine to the epsilon-amino group of ‘Lys-4’ of histone H3 (H3K4).
EGFR	Epidermal growth factor receptor	Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses.
HRAS	GTPase HRas	Involved in the activation of Ras protein signal transduction.
KRAS	GTPase KRas	Ras proteins bind GDP/GTP and possess intrinsic GTPase activity.

Protein-family classification

Druggable: 3 · Difficult: 2 · Unknown: 0 · Druggable fraction: 0.6

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	5.5×	0.168
Enzyme (other)	2	4.8×	0.168
Transcription factor	2	3.3×	0.168

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TP53	Transcription factor	no		p53_tumour_suppressor, p53-like_TF_DNA-bd_sf, p53_tetrameristn
KMT2C	Transcription factor	no		HMGI/Y_DNA-bd_CS, SET_dom, Znf_RING
EGFR	Kinase	yes	2.7.10.1	Rcpt_L-dom, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom
HRAS	Enzyme (other)	yes	3.6.5.2	Small_GTPase, Small_GTP-bd, Small_GTPase_Ras-type
KRAS	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.

5 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)	5
unknown	0

Top tissues across cohort

Tissue	Cohort genes
nipple	2
ganglionic eminence	1
tendon of biceps brachii	1
ventricular zone	1
caput epididymis	1
oocyte	1
upper arm skin	1
gingiva	1
gingival epithelium	1
skin of abdomen	1
skin of leg	1
zone of skin	1
pylorus	1
trigeminal ganglion	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TP53	223	ubiquitous	marker	ventricular zone, ganglionic eminence, tendon of biceps brachii
KMT2C	261	ubiquitous	marker	oocyte, caput epididymis, upper arm skin
EGFR	285	ubiquitous	marker	nipple, gingiva, gingival epithelium
HRAS	139	ubiquitous	marker	skin of abdomen, skin of leg, zone of skin
KRAS	298	ubiquitous	marker	trigeminal ganglion, pylorus, nipple

Protein interactions among cohort

Intra-cohort edges: 4.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TP53	22,736
EGFR	18,421
KRAS	14,509
HRAS	8,064
KMT2C	3,321

Intra-cohort edges

A	B	Sources
EGFR	HRAS	string_interaction
HRAS	TP53	string_interaction
KMT2C	TP53	intact, string_interaction
KRAS	TP53	string_interaction

Structural data

PDB: 5 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KRAS	P01116	511
EGFR	P00533	388
TP53	P04637	313
HRAS	P01112	246
KMT2C	Q8NEZ4	9

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 162. Enrichment computed across 5 evidence-associated genes (5 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 5 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
EGFR Transactivation by Gastrin	3	685.2×	8e-07	EGFR, HRAS, KRAS
GRB2 events in EGFR signaling	3	456.8×	9e-07	EGFR, HRAS, KRAS
SHC1 events in EGFR signaling	3	428.2×	9e-07	EGFR, HRAS, KRAS
Constitutive Signaling by EGFRvIII	3	428.2×	9e-07	EGFR, HRAS, KRAS
Signaling by ERBB2 ECD mutants	3	403.1×	9e-07	EGFR, HRAS, KRAS
GRB2 events in ERBB2 signaling	3	380.7×	9e-07	EGFR, HRAS, KRAS
Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants	3	342.6×	1e-06	EGFR, HRAS, KRAS
SHC1 events in ERBB2 signaling	3	285.5×	1e-06	EGFR, HRAS, KRAS
Signaling by ERBB2 TMD/JMD mutants	3	285.5×	1e-06	EGFR, HRAS, KRAS
Signaling by ERBB2 KD Mutants	3	253.8×	2e-06	EGFR, HRAS, KRAS
Signaling by RAS GAP mutants	2	1522.7×	6e-06	HRAS, KRAS
Signaling by RAS GTPase mutants	2	1522.7×	6e-06	HRAS, KRAS
Activation of RAS in B cells	2	913.6×	2e-05	HRAS, KRAS
RAS signaling downstream of NF1 loss-of-function variants	2	652.6×	3e-05	HRAS, KRAS
Estrogen-stimulated signaling through PRKCZ	2	652.6×	3e-05	HRAS, KRAS
SOS-mediated signalling	2	571.0×	4e-05	HRAS, KRAS
Activated NTRK3 signals through RAS	2	507.6×	5e-05	HRAS, KRAS
SHC-related events triggered by IGF1R	2	456.8×	6e-05	HRAS, KRAS
Activated NTRK2 signals through RAS	2	456.8×	6e-05	HRAS, KRAS
MET activates RAS signaling	2	415.3×	7e-05	HRAS, KRAS
Signaling by FGFR4 in disease	2	380.7×	7e-05	HRAS, KRAS
Activated NTRK2 signals through FRS2 and FRS3	2	380.7×	7e-05	HRAS, KRAS
Constitutive Signaling by Overexpressed ERBB2	2	380.7×	7e-05	HRAS, KRAS
p38MAPK events	2	351.4×	7e-05	HRAS, KRAS
Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants	2	351.4×	7e-05	HRAS, KRAS
Signaling by PDGFRA extracellular domain mutants	2	351.4×	7e-05	HRAS, KRAS
PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases	2	326.3×	8e-05	HRAS, KRAS
Erythropoietin activates RAS	2	304.5×	9e-05	HRAS, KRAS
Signaling by FLT3 ITD and TKD mutants	2	304.5×	9e-05	HRAS, KRAS
SHC1 events in ERBB4 signaling	2	285.5×	1e-04	HRAS, KRAS

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 5 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
Ras protein signal transduction	3	123.3×	2e-04	TP53, HRAS, KRAS
neuron apoptotic process	3	111.1×	2e-04	TP53, HRAS, KRAS
positive regulation of cellular senescence	2	518.5×	4e-04	TP53, KRAS
regulation of long-term neuronal synaptic plasticity	2	396.5×	5e-04	HRAS, KRAS
glial cell proliferation	2	354.8×	5e-04	TP53, KRAS
cellular response to gamma radiation	2	240.7×	1e-03	TP53, HRAS
fibroblast proliferation	2	156.8×	0.002	TP53, HRAS
intrinsic apoptotic signaling pathway	2	143.4×	0.002	TP53, HRAS
positive regulation of fibroblast proliferation	2	118.3×	0.002	EGFR, HRAS
cellular senescence	2	118.3×	0.002	TP53, HRAS
positive regulation of miRNA transcription	2	116.2×	0.002	TP53, EGFR
positive regulation of transcription by RNA polymerase II	4	11.9×	0.002	TP53, KMT2C, EGFR, HRAS
positive regulation of epithelial cell proliferation	2	97.7×	0.003	EGFR, HRAS
negative regulation of helicase activity	1	3370.4×	0.003	TP53
response to mineralocorticoid	1	3370.4×	0.003	KRAS
cellular response to actinomycin D	1	3370.4×	0.003	TP53
regulation of intrinsic apoptotic signaling pathway by p53 class mediator	1	3370.4×	0.003	TP53
negative regulation of G1 to G0 transition	1	3370.4×	0.003	TP53
negative regulation of cardiocyte differentiation	1	3370.4×	0.003	EGFR
MAPK cascade	2	61.3×	0.005	HRAS, KRAS
positive regulation of mitochondrial membrane permeability	1	1685.2×	0.005	TP53
oligodendrocyte apoptotic process	1	1685.2×	0.005	TP53
negative regulation of glucose catabolic process to lactate via pyruvate	1	1685.2×	0.005	TP53
negative regulation of pentose-phosphate shunt	1	1685.2×	0.005	TP53
obsolete homolactic fermentation	1	1123.5×	0.006	TP53
forebrain astrocyte development	1	1123.5×	0.006	KRAS
signal transduction by p53 class mediator	1	1123.5×	0.006	TP53
positive regulation of protein kinase C signaling	1	1123.5×	0.006	EGFR
negative regulation of miRNA processing	1	1123.5×	0.006	TP53
intrinsic apoptotic signaling pathway in response to hypoxia	1	1123.5×	0.006	TP53

Therapeutics

Drug target analysis

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

Druggability breadth: 5 of 5 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
TP53	NITROFURANTOIN
EGFR	LEVODOPA
HRAS	LONAFARNIB
KRAS	VEMURAFENIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TP53	196	4
EGFR	175	4
KRAS	11	4
HRAS	4	4
KMT2C	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
NITROFURANTOIN	4	TP53
DIOSMIN	4	TP53
VERTEPORFIN	4	TP53
CANDESARTAN CILEXETIL	4	TP53
DIENESTROL	4	TP53
CLOTRIMAZOLE	4	EGFR, TP53
COLCHICINE	4	TP53
NABUMETONE	4	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
TRIFLUPROMAZINE HYDROCHLORIDE	4	TP53
PROCHLORPERAZINE EDISYLATE	4	TP53
DEQUALINIUM CHLORIDE	4	TP53

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 3.

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

Symbol	Assays	Type breakdown
EGFR	6,531	Binding:6211, Functional:173, ADMET:138, Toxicity:9
TP53	869	Binding:775, ADMET:83, Functional:10, Toxicity:1
KRAS	861	Binding:829, Functional:32
HRAS	48	Binding:45, Functional:3
KMT2C	29	Binding:29

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
EGFR	2.7.10.1	receptor protein-tyrosine kinase
HRAS	3.6.5.2	small monomeric GTPase
KRAS	3.6.5.2	small monomeric GTPase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
TP53	869
EGFR	6,531
KRAS	861

Pharmacogenomics

Cohort genes with a PharmGKB record: 5; 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)
NITROFURANTOIN	4	TP53
DIOSMIN	4	TP53
VERTEPORFIN	4	TP53
CANDESARTAN CILEXETIL	4	TP53
DIENESTROL	4	TP53
CLOTRIMAZOLE	4	EGFR, TP53
COLCHICINE	4	TP53
NABUMETONE	4	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
TRIFLUPROMAZINE HYDROCHLORIDE	4	TP53
PROCHLORPERAZINE EDISYLATE	4	TP53
DEQUALINIUM CHLORIDE	4	TP53

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	4	TP53, EGFR, HRAS, KRAS
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	1	KMT2C

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
KMT2C	29	—

Clinical trials & evidence

Clinical trials

Clinical trials: 166.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	58
Not specified	46
PHASE1	35
PHASE1/PHASE2	16
EARLY_PHASE1	7
PHASE3	3
PHASE4	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT07426484	PHASE4	NOT_YET_RECRUITING	Cosibelimab for CSCC in Patients With Kidney Transplant or Hematologic Malignancy
NCT03969004	PHASE3	ACTIVE_NOT_RECRUITING	Study of Adjuvant Cemiplimab Versus Placebo After Surgery and Radiation Therapy in Patients With High Risk Cutaneous Squamous Cell Carcinoma
NCT06585410	PHASE3	RECRUITING	Study of Intralesional Cemiplimab in Adult Patients With Early Stage Cutaneous Squamous Cell Carcinoma
NCT06692556	PHASE3	RECRUITING	Study of a Strategy Integrating Adjuvant Radiation Therapy Versus Strategy Based on Monitoring in the Treatment of Carcinomas Spinocellular With High Risk of Recurrence
NCT02721732	PHASE2	ACTIVE_NOT_RECRUITING	Pembrolizumab in Treating Patients With Rare Tumors That Cannot Be Removed by Surgery or Are Metastatic
NCT02978625	PHASE2	ACTIVE_NOT_RECRUITING	Talimogene Laherparepvec and Nivolumab in Treating Patients With Refractory Lymphomas or Advanced or Refractory Non-melanoma Skin Cancers
NCT03944941	PHASE2	ACTIVE_NOT_RECRUITING	Avelumab With or Without Cetuximab in Treating Patients With Advanced Skin Squamous Cell Cancer
NCT04050436	PHASE2	ACTIVE_NOT_RECRUITING	Study Evaluating Cemiplimab Alone and Combined With RP1 in Treating Advanced Squamous Skin Cancer
NCT04204837	PHASE2	RECRUITING	Nivolumab for Treatment of Squamous Cell Carcinoma of the Skin
NCT04305795	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	An Open-label Study Using ASP-1929 Photoimmunotherapy in Combination With Anti-PD1 Therapy in EGFR Expressing Advanced Solid Tumors
NCT04315701	PHASE2	ACTIVE_NOT_RECRUITING	A PD-1 Checkpoint Inhibitor (Cemiplimab) for High-Risk Localized, Locally Recurrent, or Regionally Advanced Skin Cancer
NCT04349436	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Study to Investigate the Efficacy and Safety of RP1 in Adult Patients With Organ Transplants and Advanced Skin Malignancies
NCT04632433	PHASE2	ACTIVE_NOT_RECRUITING	Neoadjuvant Plus Adjuvant Treatment With Cemiplimab in Cutaneaous Squamous Cell Carcinoma
NCT05086692	PHASE1/PHASE2	RECRUITING	A Beta-only IL-2 ImmunoTherapY Study
NCT05269381	PHASE1/PHASE2	RECRUITING	Personalized Neoantigen Peptide-Based Vaccine in Combination With Pembrolizumab for Treatment of Advanced Solid Tumors
NCT05286294	PHASE2	ACTIVE_NOT_RECRUITING	Microbiota Transplant to Cancer Patients Who Have Failed Immunotherapy Using Faeces From Clinical Responders
NCT05377905	PHASE1/PHASE2	RECRUITING	Microneedle Array Plus Doxorubicin in Cutaneous Squamous Cell Cancer (cSCC)
NCT05565417	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Study of the Monoclonal Antibody IMT-009 in Patients With Advanced Solid Tumors or Lymphomas
NCT05574101	PHASE2	ACTIVE_NOT_RECRUITING	A Study of Radiation Therapy and Cemiplimab for People With Skin Cancer
NCT05620134	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Study of JK08 in Patients with Unresectable Locally Advanced or Metastatic Cancer
NCT05878288	PHASE2	ACTIVE_NOT_RECRUITING	Deep sequencIng in Cutaneous Squamous CEll caRciNomas
NCT05888844	PHASE2	ACTIVE_NOT_RECRUITING	A Study to Evaluate INCB099280 in Participants With Advanced Cutaneous Squamous Cell Carcinoma
NCT05896839	PHASE1/PHASE2	RECRUITING	Immunotherapy in Combination With Prednisone and Sirolimus for Kidney Transplant Recipients With Unresectable or Metastatic Skin Cancer
NCT05910827	PHASE1/PHASE2	RECRUITING	A Phase Ib/II Study of an Anti-HER3 Antibody, HMBD-001, With Cetuximab +/- Docetaxel in Advanced Squamous Cell Cancers
NCT05969860	PHASE2	RECRUITING	At-Home Cancer Directed Therapy Versus in Clinic for the Treatment of Patients With Advanced Cancer
NCT06223659	PHASE2	RECRUITING	EMLA Topical Cream for Treatment of Pain in Patients Receiving Intra-Dermal Technetium 99 Injections for Lymphoscintigraphy for Skin Cancers
NCT06288191	PHASE2	RECRUITING	Neoadjuvant Nivolumab and Relatlimab in Cutaneous Squamous Cell Carcinoma
NCT06418724	PHASE2	NOT_YET_RECRUITING	Neoadjuvant PD-1 Inhibitor and EGFR Inhibitor in Locally Advanced Cutaneous Squamous Cell Carcinoma
NCT06567314	PHASE2	RECRUITING	Phase 2 Study of Ivonescimab in Patients With Cutaneous Squamous Cell Carcinoma
NCT06577311	PHASE2	RECRUITING	Evaluating the Use of Photodynamic Therapy to Treat Facial Cutaneous Squamous Cell Carcinoma in Situ (SCCis)
NCT06823479	PHASE2	RECRUITING	Towards Cure Via Only Ultra-short ICB in CSCC
NCT06998342	PHASE2	RECRUITING	MOHs Surgery and Short-Course Radiation Therapy With Structured Follow-Up for Head & Neck Squamous Cell Skin Cancer
NCT07228442	PHASE2	NOT_YET_RECRUITING	L19IL2/L19TNF in Patients With Cutaneous Squamous Cell Carcinoma
NCT07288073	PHASE2	RECRUITING	TIL Therapy in cSCC and MCC
NCT07339176	PHASE1/PHASE2	RECRUITING	Intratumoral N17350 in Advanced Solid Tumors
NCT07394244	PHASE2	NOT_YET_RECRUITING	Pucotenlimab Combined With Becotatug Vedotin in Advanced Cutaneous Squamous Cell Carcinoma
NCT07455331	PHASE2	NOT_YET_RECRUITING	Flash Radiotherapy for Skin Cancer
NCT07576725	PHASE2	NOT_YET_RECRUITING	Low Dose, Reduced Frequency Nivolumab for the Treatment of Unresectable or Metastatic Cancer, AFFORD IO Trial
NCT07602842	PHASE1/PHASE2	NOT_YET_RECRUITING	A Study of IDP-001 in Advanced or Metastatic Solid Tumors
NCT00089180	PHASE2	COMPLETED	T4N5 Liposomal Lotion in Preventing The Recurrence of Nonmelanoma Skin Cancer in Patients Who Have Undergone a Kidney Transplant

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
CEMIPLIMAB	4	16
DACOMITINIB ANHYDROUS	4	3
COSIBELIMAB	4	2
DASATINIB ANHYDROUS	4	2
TALIMOGENE LAHERPAREPVEC	4	2
AMINOLEVULINIC ACID	4	1
AMIVANTAMAB	4	1
COBIMETINIB	4	1
DOCETAXEL	4	1
EVEROLIMUS	4	1
FRUQUINTINIB	4	1
FUTIBATINIB	4	1
GLATIRAMER ACETATE	4	1
LIFILEUCEL	4	1
NIACINAMIDE	4	1
PRAMLINTIDE	4	1
SIROLIMUS	4	1
RIGOSERTIB	3	2
VUSOLIMOGENE ODERPAREPVEC	3	2
BECOTATUG VEDOTIN	3	1
FAVEZELIMAB	3	1
FIANLIMAB	3	1
IVONESCIMAB	3	1
L19IL2	3	1
LINSITINIB	3	1
ONFEKAFUSP ALFA	3	1
PUCOTENLIMAB	3	1
HILTONOL	2	2
NANRILKEFUSP ALFA	2	2
DARLEUKIN	2	1

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 10 predictive associations from 10 curated evidence items; also 1 diagnostic, 1 prognostic.

Molecular subtype	Therapy	Effect	Level	CIViC
EGFR P753S	Cetuximab + Sirolimus	Sensitivity/Response	CIViC C	EID1089
HRAS G12D	Vemurafenib	Resistance	CIViC C	EID3698
HRAS G13D	Vemurafenib	Resistance	CIViC C	EID3851
HRAS G13V	Vemurafenib	Resistance	CIViC C	EID4418
HRAS Q61K	Vemurafenib	Resistance	CIViC C	EID3850
HRAS Q61L	Vemurafenib	Resistance	CIViC C	EID3848
HRAS Q61R	Vemurafenib	Resistance	CIViC C	EID3849
KRAS G12C	Vemurafenib	Resistance	CIViC C	EID3982
KRAS G12D	Vemurafenib	Resistance	CIViC C	EID3961
TP53 P278S	Vemurafenib	Resistance	CIViC C	EID4419