Skin basal cell carcinoma

Summary

Skin basal cell carcinoma (MONDO:0005341) is a cancer (an umbrella term covering 25 Mondo subtypes) with 1 cohort gene (1 CIViC-evidence somatic driver) and 257 clinical trials. Molecularly, PTCH1 Loss-of-function confers sensitivity to Vismodegib in Basal Cell Carcinoma (CIViC Level A); 24 further subtype–drug associations are mapped below. Top therapeutic interventions include vismodegib, sonidegib, and imiquimod.

At a glance

• Classification: Cancer
• Umbrella term: 25 Mondo subtypes
• Cohort genes: 1
• Clinical trials: 257
• Precision-medicine evidence (CIViC): 25 subtype–drug associations

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	skin basal cell carcinoma
Mondo ID	MONDO:0005341
DOID	DOID:2513
NCIT	C2921
SNOMED CT	254701007
UMLS	C4721806
MedGen	1648304
Is cancer (heuristic)	yes

Also known as: basal cell cancer · basal cell carcinoma · basal cell carcinoma of skin · basal cell carcinoma of the skin · basal cell epithelioma · basal cell skin carcinoma · basal cell tumor · basal cell tumour · basal cell tumour (morphologic abnormality) · BCC · malignant basal cell tumour · malignant basal cell tumour (morphologic abnormality) · skin basal cell cancer · skin basal cell carcinoma

Data availability: 1 HPO phenotype · 3 cell lines · 31 intOGen driver records.

Disease family

An umbrella term covering 25 Mondo subtypes.

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

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

Subtypes (25): penis basal cell carcinoma, scrotum basal cell carcinoma, nodular basal cell carcinoma, metatypical basal cell carcinoma, skin pigmented basal cell carcinoma, anal margin basal cell carcinoma, sebaceous basal cell carcinoma, external ear basal cell carcinoma, micronodular basal cell carcinoma, adamantinoid basal cell epithelioma, skin fibroepithelial basal cell carcinoma, morpheaform basal cell carcinoma, skin clear cell basal cell carcinoma, skin adenoid basal cell carcinoma, follicular basal cell carcinoma, skin infiltrative basal cell carcinoma, superficial multifocal basal cell carcinoma, vulva basal cell carcinoma, skin cystic basal cell carcinoma, sarcomatoid basal cell carcinoma, signet ring basal cell carcinoma, basosquamous carcinoma, salivary gland basal cell adenocarcinoma, infundibulocystic basal cell carcinoma, follicular atrophoderma-basal cell 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: 3 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
SMO	Act	BCC,GB,HCC,MBL,PAST,PLMESO,SKIN	CIViC #5365

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SMO	Orphanet:1553	Curry-Jones syndrome
SMO	Orphanet:2495	Meningioma
SMO	Orphanet:388	Hirschsprung disease

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
SMO	HGNC:11119	ENSG00000128602	Q99835	Protein smoothened	civic_evidence

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SMO	Protein smoothened	G protein-coupled receptor which associates with the patched protein (PTCH) to transduce hedgehog protein signaling.

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
GPCR	1	23.9×	0.042

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SMO	GPCR	yes		Frizzled/Smoothened_7TM, Frizzled/SFRP, GPCR_2-like_7TM

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
left ovary	1
right ovary	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SMO	225	ubiquitous	marker	ventricular zone, left ovary, right ovary

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SMO	2,882

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SMO	Q99835	15

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 12. 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
Activation of SMO	1	634.4×	0.011	SMO
BBSome-mediated cargo-targeting to cilium	1	496.5×	0.011	SMO
Cargo trafficking to the periciliary membrane	1	248.3×	0.011	SMO
Class B/2 (Secretin family receptors)	1	190.3×	0.011	SMO
Signaling by Hedgehog	1	184.2×	0.011	SMO
Hedgehog ‘off’ state	1	178.4×	0.011	SMO
Hedgehog ‘on’ state	1	158.6×	0.011	SMO
Cilium Assembly	1	108.8×	0.014	SMO
Organelle biogenesis and maintenance	1	66.0×	0.019	SMO
GPCR ligand binding	1	64.2×	0.019	SMO
Signaling by GPCR	1	40.1×	0.027	SMO
Signal Transduction	1	10.2×	0.098	SMO

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
ventral midline determination	1	16852.0×	0.001	SMO
mesenchymal to epithelial transition involved in metanephric renal vesicle formation	1	16852.0×	0.001	SMO
regulation of heart morphogenesis	1	16852.0×	0.001	SMO
negative regulation of hair follicle development	1	8426.0×	0.002	SMO
pancreas morphogenesis	1	5617.3×	0.002	SMO
regulation of cerebellar granule cell precursor proliferation	1	4213.0×	0.002	SMO
contact inhibition	1	4213.0×	0.002	SMO
epithelial-mesenchymal cell signaling	1	4213.0×	0.002	SMO
response to inositol	1	4213.0×	0.002	SMO
regulation of somatic stem cell population maintenance	1	3370.4×	0.002	SMO
cerebellar cortex morphogenesis	1	2808.7×	0.002	SMO
midgut development	1	2106.5×	0.002	SMO
spinal cord dorsal/ventral patterning	1	2106.5×	0.002	SMO
determination of left/right asymmetry in lateral mesoderm	1	1872.4×	0.002	SMO
myoblast migration	1	1872.4×	0.002	SMO
thalamus development	1	1404.3×	0.002	SMO
positive regulation of organ growth	1	1404.3×	0.002	SMO
forebrain morphogenesis	1	1404.3×	0.002	SMO
type B pancreatic cell development	1	1296.3×	0.002	SMO
atrial septum morphogenesis	1	1296.3×	0.002	SMO
negative regulation of epithelial cell differentiation	1	1203.7×	0.002	SMO
mammary gland epithelial cell differentiation	1	1203.7×	0.002	SMO
left/right axis specification	1	1203.7×	0.002	SMO
negative regulation of DNA binding	1	1123.5×	0.002	SMO
somite development	1	1123.5×	0.002	SMO
smooth muscle tissue development	1	1053.2×	0.002	SMO
astrocyte activation	1	991.3×	0.002	SMO
commissural neuron axon guidance	1	991.3×	0.002	SMO
cellular response to cholesterol	1	842.6×	0.003	SMO
dorsal/ventral neural tube patterning	1	802.5×	0.003	SMO

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
SMO	INFIGRATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SMO	11	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
INFIGRATINIB	4	SMO
SONIDEGIB	4	SMO
SONIDEGIB PHOSPHATE	4	SMO
VISMODEGIB	4	SMO
LINIFANIB	3	SMO
PATIDEGIB	3	SMO
FORETINIB	2	SMO
CEP-32496	2	SMO
TALADEGIB	2	SMO
TAK-441	1	SMO
LEQ506	1	SMO

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
SMO	131	Binding:111, Functional:20

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
SMO	131

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

8 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)
INFIGRATINIB	4	SMO
SONIDEGIB PHOSPHATE	4	SMO
LINIFANIB	3	SMO
FORETINIB	2	SMO
CEP-32496	2	SMO
TALADEGIB	2	SMO
TAK-441	1	SMO
LEQ506	1	SMO

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	SMO
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: 257.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	140
PHASE2	55
PHASE1	25
PHASE3	14
PHASE1/PHASE2	10
EARLY_PHASE1	8
PHASE4	3
PHASE2/PHASE3	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00314756	PHASE4	COMPLETED	Treatment of Nodular Basal Cell Carcinoma (BCC) With Imiquimod 5% Cream After Curettage
NCT00581425	PHASE4	COMPLETED	Intron-A/Aldara Combination Therapy for Basal Cell Carcinoma (BCC)
NCT03610022	PHASE4	COMPLETED	Relationship Between Pharmacokinetics and Safety of Vismodegib - OPTIVISMO-1
NCT05078047	PHASE3	RECRUITING	Study Comparing the Standard Administration of IO Versus the Same IO Administered Each 3 Months in Patients in Response After 6 Months of Standard IO
NCT05212246	PHASE3	NOT_YET_RECRUITING	Basal Cell Carcinoma Chemoprevention Trial
NCT00049959	PHASE3	TERMINATED	Two Studies to Determine if Verteporfin PDT is Effective & Safe in Treating Multiple Basal Cell Carcinoma of the Skin.
NCT00129519	PHASE3	COMPLETED	A Study to Evaluate the Effectiveness of Imiquimod 5% Cream for Basal Cell Carcinoma Recurrence
NCT00189241	PHASE3	COMPLETED	A Study to Evaluate Effectiveness of Imiquimod 5% Cream in Superficial Basal Cell Carcinoma
NCT00472043	PHASE3	COMPLETED	PDT With Metvix 160 mg/g Cream Versus PDT With Placebo Cream in Participants With Primary Nodular Basal Call Carcinoma
NCT00472108	PHASE3	COMPLETED	Photodynamic Therapy (PDT) With Metvix Cream 160 mg/g Versus PDT With Placebo Cream in Participants With Primary Nodular Basal Cell Carcinoma
NCT00472459	PHASE3	COMPLETED	Photodynamic Therapy (PDT) With Metvix® 160 Milligrams/Gram Cream in Organ Transplant Participants With Non-melanoma Skin Cancer
NCT00473343	PHASE3	COMPLETED	Metvix PDT in Participant With High Risk Basal Cell Carcinoma
NCT00663650	PHASE3	UNKNOWN	Periocular Basal Cell Carcinoma (BCC): Permanent vs. Frozen Section Pathological Control
NCT01212549	PHASE3	COMPLETED	Comparison of Two Schemes of Cryosurgery and Imiquimod Combination Treatment for Basal Cell Carcinoma
NCT01260987	PHASE2/PHASE3	COMPLETED	Fractional CO2 Laser Assisted Photodynamic Therapy
NCT02144077	PHASE3	COMPLETED	Safety and Efficacy Study for the Treatment of Non-Aggressive Basal Cell Carcinoma With Photodynamic Therapy
NCT03070691	PHASE2/PHASE3	WITHDRAWN	Efficacy, Safety and Tolerability of Topically Applied LDE225 Cream (Hedgehog Pathway Inhibitor) in Adult Patients With Nevoid Basal Cell Carcinoma Syndrome (NBCCS)
NCT05046262	PHASE3	UNKNOWN	Calcium Electroporation for Basal Cell Carcinomas - Proof of Concept Study
NCT06150144	PHASE3	UNKNOWN	The Efficacy and Safety of Using Intralesional 5-fluorouracil for Basal Cell Carcinoma
NCT02834013	PHASE2	ACTIVE_NOT_RECRUITING	Nivolumab and Ipilimumab in Treating Patients With Rare Tumors
NCT02978625	PHASE2	ACTIVE_NOT_RECRUITING	Talimogene Laherparepvec and Nivolumab in Treating Patients With Refractory Lymphomas or Advanced or Refractory Non-melanoma Skin Cancers
NCT03521830	PHASE2	RECRUITING	Nivolumab Alone or Plus Relatlimab or Ipilimumab for Patients With Locally-Advanced Unresectable or Metastatic Basal Cell Carcinoma
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
NCT04679480	PHASE2	ACTIVE_NOT_RECRUITING	Anti-PD1-antibody and Pulsed HHI for Advanced BCC
NCT04928222	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Placebo Microneedles in Healthy Volunteers (Part I) and Efficacy/Safety of Doxorubicin Microneedles in Basal Cell Cancer Subjects (Part II)
NCT05020912	PHASE2	RECRUITING	Alteration of the Immune Microenvironment in Basal Cell Carcinoma Following Photodynamic Therapy
NCT05086692	PHASE1/PHASE2	RECRUITING	A Beta-only IL-2 ImmunoTherapY Study
NCT05202860	PHASE2	ACTIVE_NOT_RECRUITING	Impact of Human Papillomavirus (HPV) Vaccination on Burden of Disease in Patients with Actinic Keratosis
NCT05294120	PHASE2	ACTIVE_NOT_RECRUITING	A Study on Radiation Therapy Guided by the Reflectance Confocal Microscopy (RCM)/Optical Coherence Tomography (OCT) Device in People With Basal Cell Carcinoma
NCT05561634	PHASE2	RECRUITING	Radiotherapy by Sonic Hedgehog Pathway Inhibitors in Basal Cell Carcinoma
NCT05896839	PHASE1/PHASE2	RECRUITING	Immunotherapy in Combination With Prednisone and Sirolimus for Kidney Transplant Recipients With Unresectable or Metastatic Skin Cancer
NCT05929664	PHASE2	RECRUITING	Cemiplimab Plus Fianlimab for the Treatment of Locally Advanced Head and Neck Basal Cell Carcinoma Before Surgery
NCT05969860	PHASE2	RECRUITING	At-Home Cancer Directed Therapy Versus in Clinic for the Treatment of Patients With Advanced Cancer
NCT06344052	PHASE2	RECRUITING	To Assess the Safety and Efficacy of SP-002 with Vismodegib for the Treatment of Locally Advanced Basal Cell Carcinoma
NCT06422936	PHASE2	ACTIVE_NOT_RECRUITING	Clinical Trial to Evaluate BO-112 in Patients With Basal Cell Carcinoma (BCC)
NCT06624475	PHASE2	RECRUITING	Neoadjuvant Nivolumab + Relatlimab (Opdualag) Versus Nivolumab for Resectable High-Risk Basal Cell Carcinoma
NCT06683846	PHASE2	RECRUITING	Ivonescimab in the Treatment of Multiple Advanced Tumors
NCT06981325	PHASE2	RECRUITING	Evaluation of Efficacy and Safety of Cemiplimab as First Line Treatment for Advanced Basal Cell Carcinoma (BCC) Patients
NCT07010692	PHASE1/PHASE2	RECRUITING	Treating Basal and Squamous Cell Carcinomas With Fractional Laser and Tirbanibulin Ointment
NCT07227350	PHASE2	NOT_YET_RECRUITING	L19IL2 or L19TNF or L19IL2/TNF in Patients With Basal Cell Carcinoma (BCC)

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
VISMODEGIB	4	20
SONIDEGIB	4	10
IMIQUIMOD	4	7
CEMIPLIMAB	4	2
INGENOL MEBUTATE	4	2
ITRACONAZOLE	4	2
METHYL AMINOLEVULINATE	4	2
AMINOLEVULINIC ACID	4	1
ARSENIC TRIOXIDE	4	1
CALCITRIOL	4	1
CALCIUM CHLORIDE	4	1
GLATIRAMER ACETATE	4	1
HYDROGEN PEROXIDE	4	1
MELPHALAN	4	1
RELATLIMAB	4	1
TALIMOGENE LAHERPAREPVEC	4	1
L19IL2	3	2
ONFEKAFUSP ALFA	3	2
PATIDEGIB	3	2
ALANINE	3	1
FIANLIMAB	3	1
MAXACALCITOL	3	1
VUSOLIMOGENE ODERPAREPVEC	3	1
DARLEUKIN	2	2
BMS-833923	2	1
GUSACITINIB	2	1
HILTONOL	2	1
PROGRAMMED CELL DEATH 1 LIGAND 1	2	1
REMETINOSTAT	2	1
VIDUTOLIMOD	2	1

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 25 predictive associations from 31 curated evidence items; also 2 diagnostic, 1 oncogenic.

Molecular subtype	Therapy	Effect	Level	CIViC
PTCH1 Loss-of-function	Vismodegib	Sensitivity/Response	CIViC A	EID11607
PTCH1 Loss-of-function	Sonidegib	Sensitivity/Response	CIViC A	EID11608
SMO Mutation	Vismodegib + Sonidegib	Resistance	CIViC B	EID1477
SMO Mutation	Vismodegib	Resistance	CIViC B	EID746
PTCH1 Q17X	Vismodegib	Sensitivity/Response	CIViC C	EID4684
PTCH1 Q787X	Vismodegib	Sensitivity/Response	CIViC C	EID4683
PTCH1 W170X	Vismodegib	Sensitivity/Response	CIViC C	EID4681
PTCH1 W712X	Vismodegib	Sensitivity/Response	CIViC C	EID4682
SMO L412F	Vismodegib	Resistance	CIViC C	EID4654 +2
SMO V321M	Vismodegib	Resistance	CIViC C	EID4660 +2
SMO W535L	Vismodegib	Resistance	CIViC C	EID3735 +1
SMO D473G	Vismodegib	Resistance	CIViC C	EID4634
SMO D473Y	Vismodegib	Resistance	CIViC C	EID4635
SMO G497W	Vismodegib	Resistance	CIViC C	EID4675
SMO S278I	Vismodegib	Resistance	CIViC C	EID4636
SMO W281L	Vismodegib	Resistance	CIViC C	EID4674
SMO Mutation	Arsenic Trioxide + PSI	Sensitivity/Response	CIViC D	EID747
SMO W281C	Vismodegib	Resistance	CIViC D	EID4637 +1
SMO A459V	Vismodegib	Resistance	CIViC D	EID4679
SMO C469Y	Vismodegib	Resistance	CIViC D	EID4677
SMO D473H	Vismodegib	Resistance	CIViC D	EID755
SMO I408V	Vismodegib	Resistance	CIViC D	EID4676
SMO Q477E	Vismodegib	Resistance	CIViC D	EID4639
SMO S533N	Vismodegib	Resistance	CIViC D	EID4680
SMO T241M	Vismodegib	Resistance	CIViC D	EID4678