Transitional cell carcinoma

Summary

Transitional cell carcinoma (MONDO:0006474) is a cancer (an umbrella term covering 9 Mondo subtypes) with 7 cohort genes (7 CIViC-evidence somatic drivers) and 43 clinical trials. The dominant Reactome pathway is PIP3 activates AKT signaling (5 cohort genes). Molecularly, FGFR3::v Fusion confers sensitivity to Erdafitinib in Transitional Cell Carcinoma (CIViC Level A); 31 further subtype–drug associations are mapped below. Top therapeutic interventions include gemcitabine, mitomycin, and vinflunine.

At a glance

• Classification: Cancer
• Umbrella term: 9 Mondo subtypes
• Cohort genes: 7
• Clinical trials: 43
• Precision-medicine evidence (CIViC): 32 subtype–drug associations

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	transitional cell carcinoma
Mondo ID	MONDO:0006474
EFO	EFO:1000601
MeSH	D002295
DOID	DOID:2671
NCIT	C2930
UMLS	C0007138
MedGen	2875
GARD	0007794
Is cancer (heuristic)	yes

Also known as: carcinoma of transitional epithelial cell · carcinoma of urothelial cell · carcinoma, urothelial, malignant · transitional carcinoma · transitional cell carcinoma · transitional cell neoplasm · transitional cell tumor · transitional cell tumour · transitional epithelial cell carcinoma · urothelial cell carcinoma

Disease family

An umbrella term covering 9 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › cancer › carcinoma › transitional cell carcinoma

Related subtypes (48): retroperitoneum carcinoma, head and neck carcinoma, peritoneal carcinoma, neuroendocrine carcinoma, laryngeal carcinoma, bone carcinoma, carcinoma ex pleomorphic adenoma, scrotal carcinoma, skin carcinoma, malignant myoepithelioma, trachea carcinoma, epithelial-myoepithelial carcinoma, lipid-rich carcinoma, comedocarcinoma, in situ carcinoma, adenocarcinoma, urinary bladder carcinoma, breast carcinoma, squamous cell carcinoma, lung carcinoma, prostate carcinoma, renal carcinoma, uterine carcinoma, vulvar carcinoma, large cell carcinoma, undifferentiated carcinoma, basaloid carcinoma, cribriform carcinoma, digestive system carcinoma, fallopian tube carcinoma, penile carcinoma, sarcomatoid carcinoma, thymic carcinoma, ureter carcinoma, papillary carcinoma, Krebs 2 carcinoma, thyroid gland carcinoma, vaginal carcinoma, choroid plexus carcinoma, malignant epithelial tumor of ovary, mucin-producing carcinoma, basal cell carcinoma, carcinoma of urethra, combined carcinoid and adenocarcinoma, secondary carcinoma, invasive carcinoma, glycogen-rich carcinoma, lymph node carcinoma

Subtypes (9): Bartholin gland transitional cell carcinoma, endometrial transitional cell carcinoma, fallopian tube transitional cell carcinoma, primary prostate urothelial carcinoma, sarcomatoid transitional cell carcinoma, ovarian transitional cell carcinoma, papillary transitional cell carcinoma, transitional cell carcinoma of the corpus uteri, urothelial 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
ERBB2	Act	BLCA,BRCA,CESC,CHOL,COADREAD,EGC,ESCA,ESCC,LMS,LUAD,NSCLC,OVT,PRCC,READ,STAD,UCEC	CIViC #20
ERBB3	Act	BLCA,BRCA,CESC,CHOL,COADREAD,NBL,PRAD,STAD,UCEC,UCS,UTUC	CIViC #1733
FGFR2	Act	BRCA,CHOL,LUSC,SACA,UCEC	CIViC #22
FGFR3	Act	BLADDER,BLCA,HNSC,LUSC,PCM,PLMESO,UTUC	CIViC #23
MTOR	Act	BLCA,BRCA,CCRCC,CHRCC,CLLSLL,COADREAD,HCC,LGGNOS,PANET,RCC,UCEC	CIViC #2073
MSH2			CIViC #3628
MSH6			CIViC #2478

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ERBB2	Orphanet:213726	Serous carcinoma of the corpus uteri
ERBB2	Orphanet:2800	Extramammary Paget disease
ERBB2	Orphanet:388	Hirschsprung disease
ERBB2	Orphanet:99976	Adenocarcinoma of the oesophagus and oesophagogastric junction
ERBB3	Orphanet:137776	Lethal congenital contracture syndrome type 2
ERBB3	Orphanet:388	Hirschsprung disease
FGFR2	Orphanet:1540	Jackson-Weiss syndrome
FGFR2	Orphanet:1555	Cutis gyrata-acanthosis nigricans-craniosynostosis syndrome
FGFR2	Orphanet:168624	Familial scaphocephaly syndrome, McGillivray type
FGFR2	Orphanet:207	Crouzon syndrome
FGFR2	Orphanet:2363	Lacrimoauriculodentodigital syndrome
FGFR2	Orphanet:313855	FGFR2-related bent bone dysplasia
FGFR2	Orphanet:596008	Antley-Bixler syndrome without genital anomaly or disorder of steroidogenesis
FGFR2	Orphanet:794	Saethre-Chotzen syndrome
FGFR2	Orphanet:87	Apert syndrome
FGFR2	Orphanet:93258	Pfeiffer syndrome type 1
FGFR2	Orphanet:93259	Pfeiffer syndrome type 2
FGFR2	Orphanet:93260	Pfeiffer syndrome type 3
FGFR3	Orphanet:15	Achondroplasia
FGFR3	Orphanet:1860	Thanatophoric dysplasia type 1
FGFR3	Orphanet:2363	Lacrimoauriculodentodigital syndrome
FGFR3	Orphanet:251576	Gliosarcoma
FGFR3	Orphanet:251579	Giant cell glioblastoma
FGFR3	Orphanet:35099	Non-syndromic bicoronal craniosynostosis
FGFR3	Orphanet:429	Hypochondroplasia
FGFR3	Orphanet:53271	Muenke syndrome
FGFR3	Orphanet:794	Saethre-Chotzen syndrome
FGFR3	Orphanet:85164	Camptodactyly-tall stature-scoliosis-hearing loss syndrome
FGFR3	Orphanet:85165	Severe achondroplasia-developmental delay-acanthosis nigricans syndrome
FGFR3	Orphanet:93262	Crouzon syndrome-acanthosis nigricans syndrome
FGFR3	Orphanet:93274	Thanatophoric dysplasia type 2
MTOR	Orphanet:269001	Isolated focal cortical dysplasia type IIa
MTOR	Orphanet:269008	Isolated focal cortical dysplasia type IIb
MTOR	Orphanet:457485	Macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome
MTOR	Orphanet:99802	Hemimegalencephaly
MSH2	Orphanet:144	Lynch syndrome
MSH2	Orphanet:252202	Constitutional mismatch repair deficiency syndrome
MSH6	Orphanet:144	Lynch syndrome
MSH6	Orphanet:252202	Constitutional mismatch repair deficiency syndrome

Cohort genes → proteins

7 cohort genes, 7 distinct canonical proteins.

Evidence partition

Subset	Genes
civic_only	7

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ERBB2	HGNC:3430	ENSG00000141736	P04626	Receptor tyrosine-protein kinase erbB-2	civic_evidence
ERBB3	HGNC:3431	ENSG00000065361	P21860	Receptor tyrosine-protein kinase erbB-3	civic_evidence
FGFR2	HGNC:3689	ENSG00000066468	P21802	Fibroblast growth factor receptor 2	civic_evidence
FGFR3	HGNC:3690	ENSG00000068078	P22607	Fibroblast growth factor receptor 3	civic_evidence
MTOR	HGNC:3942	ENSG00000198793	P42345	Serine/threonine-protein kinase mTOR	civic_evidence
MSH2	HGNC:7325	ENSG00000095002	P43246	DNA mismatch repair protein Msh2	civic_evidence
MSH6	HGNC:7329	ENSG00000116062	P52701	DNA mismatch repair protein Msh6	civic_evidence

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ERBB2	Receptor tyrosine-protein kinase erbB-2	Protein tyrosine kinase that is part of several cell surface receptor complexes, but that apparently needs a coreceptor for ligand binding.
ERBB3	Receptor tyrosine-protein kinase erbB-3	Tyrosine-protein kinase that plays an essential role as cell surface receptor for neuregulins.
FGFR2	Fibroblast growth factor receptor 2	Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation, migration and apoptosis, and in the regulation of embryonic de…
FGFR3	Fibroblast growth factor receptor 3	Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation and apoptosis.
MTOR	Serine/threonine-protein kinase mTOR	Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
MSH2	DNA mismatch repair protein Msh2	Component of the post-replicative DNA mismatch repair system (MMR).
MSH6	DNA mismatch repair protein Msh6	Component of the post-replicative DNA mismatch repair system (MMR).

Protein-family classification

Druggable: 5 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.71

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	5	19.8×	2e-06
Other/Unknown	2	0.5×	0.968

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ERBB2	Kinase	yes	2.7.10.1	Rcpt_L-dom, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom
ERBB3	Kinase	yes	2.7.10.1	Rcpt_L-dom, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom
FGFR2	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Ig_sub2
FGFR3	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Ig_sub2
MTOR	Kinase	yes		PI3/4_kinase_cat_dom, PIK-rel_kinase_FAT, FATC_dom
MSH2	Other/Unknown	no		DNA_mismatch_repair_MutS_C, DNA_mismatch_repair_MutS-lik_N, DNA_mismatch_repair_MutS_core
MSH6	Other/Unknown	no		PWWP_dom, DNA_mismatch_repair_MutS_C, DNA_mismatch_repair_MutS-lik_N

Expression context

Cohort genes with no expression data: 0.

7 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)	7
unknown	0

Top tissues across cohort

Tissue	Cohort genes
ventricular zone	2
lower esophagus mucosa	1
right uterine tube	1
sural nerve	1
dorsal root ganglion	1
jejunal mucosa	1
trigeminal ganglion	1
C1 segment of cervical spinal cord	1
corpus callosum	1
spinal cord	1
skin of hip	1
upper arm skin	1
upper leg skin	1
cerebellar hemisphere	1
primordial germ cell in gonad	1
right hemisphere of cerebellum	1
oocyte	1
secondary oocyte	1
embryo	1
ganglionic eminence	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ERBB2	276	ubiquitous	marker	lower esophagus mucosa, right uterine tube, sural nerve
ERBB3	274	broad	marker	trigeminal ganglion, jejunal mucosa, dorsal root ganglion
FGFR2	272	broad	marker	C1 segment of cervical spinal cord, spinal cord, corpus callosum
FGFR3	262	broad	marker	upper leg skin, skin of hip, upper arm skin
MTOR	207	ubiquitous	marker	primordial germ cell in gonad, right hemisphere of cerebellum, cerebellar hemisphere
MSH2	278	ubiquitous	marker	secondary oocyte, oocyte, ventricular zone
MSH6	293	ubiquitous	marker	ventricular zone, embryo, ganglionic eminence

Protein interactions among cohort

Intra-cohort edges: 2.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ERBB2	9,659
MTOR	9,490
MSH2	4,537
ERBB3	4,511
FGFR3	4,510
MSH6	4,091
FGFR2	449

Intra-cohort edges

A	B	Sources
ERBB2	ERBB3	biogrid_interaction, intact, string_interaction
MSH2	MSH6	biogrid_interaction, intact, string_interaction

Structural data

PDB: 7 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MTOR	P42345	70
ERBB2	P04626	63
FGFR2	P21802	63
MSH2	P43246	30
ERBB3	P21860	23
FGFR3	P22607	15
MSH6	P52701	8

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 109. Enrichment computed across 7 evidence-associated genes (7 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 7 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
PIP3 activates AKT signaling	5	47.7×	2e-06	ERBB2, ERBB3, FGFR2, FGFR3, MTOR
Constitutive Signaling by Aberrant PI3K in Cancer	4	72.5×	7e-06	ERBB2, ERBB3, FGFR2, FGFR3
Defective Mismatch Repair Associated With MSH6	2	1631.4×	1e-05	MSH2, MSH6
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	4	55.3×	1e-05	ERBB2, ERBB3, FGFR2, FGFR3
Defective Mismatch Repair Associated With MSH2	2	1087.6×	2e-05	MSH2, MSH6
Mismatch Repair	2	815.7×	3e-05	MSH2, MSH6
Diseases of Mismatch Repair (MMR)	2	815.7×	3e-05	MSH2, MSH6
RAF/MAP kinase cascade	4	34.9×	3e-05	ERBB2, ERBB3, FGFR2, FGFR3
GRB7 events in ERBB2 signaling	2	543.8×	6e-05	ERBB2, ERBB3
Downregulation of ERBB2:ERBB3 signaling	2	233.1×	3e-04	ERBB2, ERBB3
Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha)	2	233.1×	3e-04	MSH2, MSH6
ERBB2 Activates PTK6 Signaling	2	233.1×	3e-04	ERBB2, ERBB3
ERBB2 Regulates Cell Motility	2	203.9×	3e-04	ERBB2, ERBB3
PI3K events in ERBB2 signaling	2	191.9×	3e-04	ERBB2, ERBB3
Diseases of DNA repair	2	163.1×	4e-04	MSH2, MSH6
SHC1 events in ERBB2 signaling	2	135.9×	6e-04	ERBB2, ERBB3
Signaling by ERBB2 TMD/JMD mutants	2	135.9×	6e-04	ERBB2, ERBB3
Signaling by ERBB2 KD Mutants	2	120.8×	7e-04	ERBB2, ERBB3
Downregulation of ERBB2 signaling	2	108.8×	8e-04	ERBB2, ERBB3
Signaling by ERBB2	2	98.9×	9e-04	ERBB2, ERBB3
PI3K Cascade	2	77.7×	0.001	FGFR2, FGFR3
Signaling by FGFR2 amplification mutants	1	1631.4×	0.003	FGFR2
t(4;14) translocations of FGFR3	1	1631.4×	0.003	FGFR3
Signaling by FGFR2 fusions	1	1631.4×	0.003	FGFR2
Signaling by FGFR3 fusions in cancer	1	1631.4×	0.003	FGFR3
Defective Mismatch Repair Associated With MSH3	1	815.7×	0.005	MSH2
PLCG1 events in ERBB2 signaling	1	407.9×	0.007	ERBB2
Drug-mediated inhibition of ERBB2 signaling	1	407.9×	0.007	ERBB2
Resistance of ERBB2 KD mutants to trastuzumab	1	407.9×	0.007	ERBB2
Resistance of ERBB2 KD mutants to sapitinib	1	407.9×	0.007	ERBB2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 7 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
somatic recombination of immunoglobulin gene segments	2	1203.7×	1e-04	MSH2, MSH6
positive regulation of MAPK cascade	4	46.1×	1e-04	ERBB2, ERBB3, FGFR2, FGFR3
positive regulation of phospholipase activity	2	963.0×	1e-04	FGFR2, FGFR3
positive regulation of epithelial cell proliferation	3	104.7×	1e-04	ERBB2, ERBB3, FGFR2
endochondral bone growth	2	481.5×	3e-04	FGFR2, FGFR3
ERBB2-ERBB3 signaling pathway	2	481.5×	3e-04	ERBB2, ERBB3
negative regulation of DNA recombination	2	321.0×	5e-04	MSH2, MSH6
Schwann cell development	2	300.9×	5e-04	ERBB2, ERBB3
somatic hypermutation of immunoglobulin genes	2	300.9×	5e-04	MSH2, MSH6
isotype switching	2	240.7×	7e-04	MSH2, MSH6
mismatch repair	2	185.2×	0.001	MSH2, MSH6
bone morphogenesis	2	172.0×	0.001	FGFR2, FGFR3
regulation of ERK1 and ERK2 cascade	2	166.0×	0.001	ERBB2, FGFR2
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	3	33.6×	0.001	ERBB3, FGFR3, MTOR
germ cell development	2	130.1×	0.002	MTOR, MSH2
determination of adult lifespan	2	123.5×	0.002	MSH2, MSH6
peptidyl-tyrosine phosphorylation	2	120.4×	0.002	ERBB2, FGFR2
oligodendrocyte differentiation	2	120.4×	0.002	ERBB2, MTOR
meiotic mismatch repair	1	2407.4×	0.003	MSH6
somatic recombination of immunoglobulin genes involved in immune response	1	2407.4×	0.003	MSH2
fibroblast growth factor receptor signaling pathway involved in negative regulation of apoptotic process in bone marrow cell	1	2407.4×	0.003	FGFR2
fibroblast growth factor receptor signaling pathway involved in hemopoiesis	1	2407.4×	0.003	FGFR2
fibroblast growth factor receptor signaling pathway involved in positive regulation of cell proliferation in bone marrow	1	2407.4×	0.003	FGFR2
negative regulation of developmental growth	1	2407.4×	0.003	FGFR3
lateral sprouting from an epithelium	1	2407.4×	0.003	FGFR2
positive regulation of SCF-dependent proteasomal ubiquitin-dependent catabolic process	1	2407.4×	0.003	MTOR
fibroblast growth factor receptor signaling pathway	2	81.6×	0.003	FGFR2, FGFR3
bone mineralization	2	77.7×	0.003	FGFR2, FGFR3
myelination	2	71.9×	0.003	ERBB2, ERBB3
epidermal growth factor receptor signaling pathway	2	70.8×	0.003	ERBB2, ERBB3

Therapeutics

Drugs indicated for this disease

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

Drug	Development status
Atezolizumab	Approved (phase 4)
Enfortumab Vedotin	Approved (phase 4)
Nivolumab	Approved (phase 4)
Pembrolizumab	Approved (phase 4)
Mitomycin	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Cabazitaxel, Dactolisib, Everolimus, Oxaliplatin, Vinflunine.

Drug target analysis

Approved (phase 4): 5 · Phase ≥3: 5 · Phased (≥1): 6 · Undrugged: 1

Druggability breadth: 7 of 7 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
ERBB2	CLOTRIMAZOLE
ERBB3	MOBOCERTINIB
FGFR2	PONATINIB
FGFR3	PONATINIB
MTOR	SALMETEROL XINAFOATE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MTOR	164	4
ERBB2	83	4
FGFR3	64	4
FGFR2	59	4
ERBB3	23	4
MSH6	1	2
MSH2	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
CLOTRIMAZOLE	4	ERBB2
ERLOTINIB HYDROCHLORIDE	4	ERBB2
PONATINIB	4	ERBB2, FGFR2, FGFR3
AFATINIB	4	ERBB2, ERBB3
LAPATINIB DITOSYLATE	4	ERBB2
SORAFENIB	4	ERBB2, FGFR2, FGFR3
NERATINIB	4	ERBB2, ERBB3
IBRUTINIB	4	ERBB2, FGFR2
AFATINIB DIMALEATE	4	ERBB2
CABOZANTINIB	4	ERBB2
DACOMITINIB	4	ERBB2
DACOMITINIB ANHYDROUS	4	ERBB2
VANDETANIB	4	ERBB2, ERBB3, FGFR2, FGFR3
TRIBROMSALAN	4	ERBB2
BOSUTINIB	4	ERBB2, ERBB3
BITHIONOL	4	ERBB2
ASTEMIZOLE	4	ERBB2
EBASTINE	4	ERBB2, MTOR
OSIMERTINIB	4	ERBB2, ERBB3
BRIGATINIB	4	ERBB2, FGFR2, FGFR3
ACALABRUTINIB	4	ERBB2
ZANUBRUTINIB	4	ERBB2
TUCATINIB	4	ERBB2
TIRABRUTINIB	4	ERBB2
PACLITAXEL	4	ERBB2, MTOR
LAZERTINIB	4	ERBB2
HEXACHLOROPHENE	4	ERBB2
DOXORUBICIN	4	ERBB2
DASATINIB	4	ERBB2, ERBB3, FGFR2, FGFR3, MTOR
ERLOTINIB	4	ERBB2, ERBB3, FGFR2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 4.

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

Symbol	Assays	Type breakdown
MTOR	1,375	Binding:1335, Functional:37, ADMET:2, Toxicity:1
ERBB2	1,221	Binding:1136, Functional:79, ADMET:6
FGFR3	975	Binding:948, Functional:18, ADMET:9
FGFR2	966	Binding:940, Functional:22, ADMET:4
ERBB3	169	Binding:169
MSH6	10	Binding:10
MSH2	9	Binding:9

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ERBB2	2.7.10.1	receptor protein-tyrosine kinase
ERBB3	2.7.10.1	receptor protein-tyrosine kinase
FGFR2	2.7.10.1	receptor protein-tyrosine kinase
FGFR3	2.7.10.1	receptor protein-tyrosine kinase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
ERBB2	1,221
ERBB3	169
FGFR2	966
FGFR3	975
MTOR	1,375

Pharmacogenomics

Cohort genes with a PharmGKB record: 7; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Drug repurposing candidates

29 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)
CLOTRIMAZOLE	4	ERBB2
ERLOTINIB HYDROCHLORIDE	4	ERBB2
PONATINIB	4	ERBB2, FGFR2, FGFR3
AFATINIB	4	ERBB2, ERBB3
LAPATINIB DITOSYLATE	4	ERBB2
SORAFENIB	4	ERBB2, FGFR2, FGFR3
NERATINIB	4	ERBB2, ERBB3
IBRUTINIB	4	ERBB2, FGFR2
AFATINIB DIMALEATE	4	ERBB2
CABOZANTINIB	4	ERBB2
DACOMITINIB	4	ERBB2
DACOMITINIB ANHYDROUS	4	ERBB2
TRIBROMSALAN	4	ERBB2
BOSUTINIB	4	ERBB2, ERBB3
BITHIONOL	4	ERBB2
ASTEMIZOLE	4	ERBB2
EBASTINE	4	ERBB2, MTOR
OSIMERTINIB	4	ERBB2, ERBB3
BRIGATINIB	4	ERBB2, FGFR2, FGFR3
ACALABRUTINIB	4	ERBB2
ZANUBRUTINIB	4	ERBB2
TUCATINIB	4	ERBB2
TIRABRUTINIB	4	ERBB2
PACLITAXEL	4	ERBB2, MTOR
LAZERTINIB	4	ERBB2
HEXACHLOROPHENE	4	ERBB2
DOXORUBICIN	4	ERBB2
DASATINIB	4	ERBB2, ERBB3, FGFR2, FGFR3, MTOR
ERLOTINIB	4	ERBB2, ERBB3, FGFR2

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	5	ERBB2, ERBB3, FGFR2, FGFR3, MTOR
B	Phased (≥1) drug, not yet approved	1	MSH6
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	MSH2

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)
MSH2	9	—

Clinical trials & evidence

Clinical trials

Clinical trials: 43.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	18
Not specified	12
PHASE3	5
PHASE2/PHASE3	4
PHASE1	3
PHASE1/PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06462001	PHASE3	ACTIVE_NOT_RECRUITING	BCG + MMC: Adding Mitomycin C to BCG in High-risk, Non-muscle-invasive Bladder Cancer
NCT00389155	PHASE2/PHASE3	COMPLETED	First-Line Treatment of Advanced Bladder Cancer Randomized vs. Gemcitabine ± Vinflunine in Patients Ineligible to Receive Cisplatin-Based Therapy
NCT01310803	PHASE3	TERMINATED	Multi-center Study to Evaluate the Efficacy and Safety of Maintenance Therapy With Valrubicin Versus no Maintenance, in Subjects Treated With Valrubicin Induction for Carcinoma in Situ (CIS) of the Bladder
NCT01438112	PHASE2/PHASE3	TERMINATED	Efficacy Study of Recombinant Adenovirus for Non Muscle Invasive Bladder Cancer
NCT01668459	PHASE2/PHASE3	COMPLETED	Treatment of Locally Advanced or Metastatic Transitional Cell Carcinoma With Cabazitaxel
NCT03193788	PHASE3	UNKNOWN	Pemetrexed Maintenance in Patients With Urothelial Carcinoma Who Completed First Line Platinum-based Chemotherapy
NCT03296306	PHASE3	UNKNOWN	Four Cycles Versus Six Cycles of Cisplatin-based Chemotherapy in Metastatic Urothelial Carcinoma
NCT04006691	PHASE3	WITHDRAWN	Efficacy and Safety of UGN-101 in Recurrent Patients
NCT05322187	PHASE2/PHASE3	UNKNOWN	Sequential PD-1/PD-L1 Inhibitor and LENvatinib in TLCT and Refractory Hepatoblastoma After Chemotherapy
NCT02420847	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Ixazomib Citrate With Gemcitabine Hydrochloride and Doxorubicin Hydrochloride in Treating Patients With Urothelial Cancer That is Metastatic or Cannot Be Removed by Surgery
NCT02834013	PHASE2	ACTIVE_NOT_RECRUITING	Nivolumab and Ipilimumab in Treating Patients With Rare Tumors
NCT03047213	PHASE2	ACTIVE_NOT_RECRUITING	Sapanisertib in Treating Patients With Locally Advanced or Metastatic Bladder Cancer With TSC1 and/or TSC2 Mutations
NCT00101608	PHASE2	COMPLETED	Vinflunine in Patients With Locally Advanced or Metastatic Transitional Cell Carcinoma of the Urothelium
NCT00154687	PHASE2	COMPLETED	Weekly TP-HDFL in the Treatment of Advanced TCC
NCT00173862	PHASE2	COMPLETED	Gemcitabine and Ifosfamide As a Second-Line Systemic Chemotherapy for Cisplatin -Failed Advanced TCC
NCT00633789	PHASE2	COMPLETED	Phase II Study of Brivanib (BMS-582664) to Treat Multiple Tumor Types
NCT00683059	PHASE2	COMPLETED	Single Agent Abraxane as Second Line Therapy in Bladder Cancer
NCT00696007	PHASE2	WITHDRAWN	Neoadjuvant Chemotherapy Plus Nephroureterectomy for Locally Advanced Upper Tract Transitional Cell Cancer
NCT00714025	PHASE2	COMPLETED	A Single Arm, Multicenter, Phase II Trial of RAD001 as Monotherapy in the Palliative Treatment of Patients With TCC After Failure of Chemotherapy
NCT00805129	PHASE2	COMPLETED	Everolimus (RAD001) in Metastatic Transitional Cell Carcinoma of the Urothelium
NCT00880334	PHASE2	COMPLETED	Randomized Study of Docetaxel +/- Vandetanib in Metastatic TCC
NCT01215136	PHASE2	TERMINATED	First-line Everolimus +/- Paclitaxel for Cisplatin-ineligible Patients With Advanced Urothelial Carcinoma
NCT02109328	PHASE2	COMPLETED	Alisertib in Chemotherapy-pretreated Urothelial Cancer
NCT02581982	PHASE2	COMPLETED	Paclitaxel and Pembrolizumab in Treating Patients With Refractory Metastatic Urothelial Cancer
NCT02887248	PHASE2	TERMINATED	Nab-paclitaxel Plus Gemcitabine as First-line Therapy for Cisplatin-ineligible or Cisplatin-incurable Advanced Urothelial Carcinoma
NCT03219775	PHASE2	UNKNOWN	Tailored ImmunoTherapy Approach With Nivolumab in Subjects With Metastatic or Advanced Transitional Cell Carcinoma
NCT04179110	PHASE2	WITHDRAWN	Study of Pembrolizumab and Ramucirumab in Pts With Progressive TCC After Treatment With an Immune Checkpoint Inhibitor
NCT04878250	PHASE2	UNKNOWN	Preoperative Bintrafusp Alfa in Operable Urothelial Carcinoma of the Bladder
NCT00070070	PHASE1	COMPLETED	Vaccine Therapy in Treating Patients With Transitional Cell Carcinomas
NCT00623831	PHASE1	COMPLETED	A Phase 1 Study of Mixed Bacteria Vaccine (MBV) in Patients With Tumors Expressing NY-ESO-1 Antigen
NCT03927573	PHASE1	TERMINATED	Study With Bispecific Antibody Engaging T-cells, in Patients With Progressive Cancer Diseases With Positive PSCA Marker
NCT04811846	Not specified	ACTIVE_NOT_RECRUITING	CTC Quantification During TURBT and PKVBT of Transitional Cell Carcinoma in Purging Fluid and Blood
NCT07485114	Not specified	RECRUITING	Association Between Galectin-3 Levels and Outcomes in Patients With Renal Cell Carcinoma, Transitional Cell Carcinoma , Non Small Cell Lung Cancer, and Hepatocellular Carcinoma, Treated With PD-1/PDL-1 Inhibitors
NCT00216801	Not specified	COMPLETED	Relationship of Ochratoxin A to Upper Urologic Cancers
NCT00612326	Not specified	COMPLETED	Feasibility Evaluation of Magnetic Resonance Imaging and Positron Emission Tomography for Bladder Cancer Diagnosis and Staging
NCT01103544	Not specified	COMPLETED	JAVLOR® Online Non-Interventional Trial
NCT01395225	Not specified	COMPLETED	Lymph Node Processing Protocol for Radical Cystectomy and Pelvic Lymph Node Dissection in Bladder Cancer
NCT02160600	Not specified	COMPLETED	Dual Energy CT vs Standard Triple Phase CT-A Randomised Control Trial
NCT02471547	Not specified	UNKNOWN	Intravesically Heated Thermo-chemotherapy With Mitomycin-C Prior to TURBT
NCT03238664	Not specified	WITHDRAWN	Robot-Assisted Laparoscopic High-Intensity Focused Ultrasound and Radical Cystectomy for Thermal Ablation of Muscle Invasive Cells in Patients With Bladder Tumors

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
GEMCITABINE	4	4
MITOMYCIN	4	2
VINFLUNINE	4	2
CABAZITAXEL	4	1
ERDAFITINIB	4	1
FOLIC ACID	4	1
IXAZOMIB CITRATE	4	1
PEMETREXED	4	1
RAMUCIRUMAB	4	1
VANDETANIB	4	1
ALISERTIB	3	1
BINTRAFUSP ALFA	3	1
BRIVANIB	3	1
NY-ESO-1	2	1
SAPANISERTIB	2	1
CHEMBL1813256	0	1
CHEMBL3962632	0	1
CHEMBL3991933	0	1

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 32 predictive associations from 35 curated evidence items; also 2 oncogenic.

Molecular subtype	Therapy	Effect	Level	CIViC
FGFR3::v Fusion	Erdafitinib	Sensitivity/Response	CIViC A	EID7262 +1
FGFR2 Mutation OR FGFR2::v Fusion OR FGFR2::? Fusion	Erdafitinib	Sensitivity/Response	CIViC A	EID7261
FGFR2::v Fusion	Erdafitinib	Sensitivity/Response	CIViC A	EID7423
FGFR3 G370C	Erdafitinib	Sensitivity/Response	CIViC A	EID7307
FGFR3 Mutation	Erdafitinib	Sensitivity/Response	CIViC A	EID7422
FGFR3 R248C	Erdafitinib	Sensitivity/Response	CIViC A	EID7305
FGFR3 S249C	Erdafitinib	Sensitivity/Response	CIViC A	EID7306
FGFR3 Y373C	Erdafitinib	Sensitivity/Response	CIViC A	EID7308
ERBB2 Amplification	Afatinib	Sensitivity/Response	CIViC B	EID7810
ERBB3 G284R	Afatinib	Sensitivity/Response	CIViC B	EID1748
ERBB3 R103G	Afatinib	Sensitivity/Response	CIViC B	EID1747
ERBB3 V104M	Afatinib	Sensitivity/Response	CIViC B	EID1746
FGFR3 G370C	Infigratinib	Sensitivity/Response	CIViC B	EID6414
FGFR3 R248C	Infigratinib	Sensitivity/Response	CIViC B	EID6410
FGFR3 S249C	Infigratinib	Sensitivity/Response	CIViC B	EID6404
FGFR3 S249C	Pazopanib	Sensitivity/Response	CIViC C	EID1603 +1
FGFR3 Y373C	Infigratinib	Sensitivity/Response	CIViC C	EID6411 +1
FGFR2::BICC1 Fusion	Erdafitinib	Sensitivity/Response	CIViC C	EID1917
FGFR3 A391E	AZD-4547	Sensitivity/Response	CIViC C	EID8315
FGFR3 F384L	Infigratinib	Sensitivity/Response	CIViC C	EID6415
FGFR3 G380R	Infigratinib	Sensitivity/Response	CIViC C	EID6413
FGFR3 R248C	Dovitinib	Sensitivity/Response	CIViC C	EID8319
FGFR3::TACC3 Fusion	Infigratinib	Sensitivity/Response	CIViC C	EID6409
MSH2 Loss	Anti-PD-1 Monoclonal Antibody MEDI0680 + Durvalumab	Sensitivity/Response	CIViC C	EID1877
MSH6 LOSS	Anti-PD-1 Monoclonal Antibody MEDI0680 + Durvalumab	Sensitivity/Response	CIViC C	EID1878
MTOR E2014K AND MTOR E2419K	Pazopanib + Everolimus	Sensitivity/Response	CIViC C	EID1438
NRF1::BRAF Fusion	Trametinib	Sensitivity/Response	CIViC C	EID7763
FGFR3 L608V	Infigratinib	Resistance	CIViC C	EID6407
FGFR3 V555L	Infigratinib	Resistance	CIViC C	EID6405
FGFR3 V555M	Infigratinib	Resistance	CIViC C	EID6406

+2 more predictive associations (showing top 30 by evidence level).