Bladder transitional cell carcinoma

Summary

Bladder transitional cell carcinoma (MONDO:0005611) is a cancer (an umbrella term covering 5 Mondo subtypes) with 8 cohort genes (8 CIViC-evidence somatic drivers) and 91 clinical trials. Molecularly, CD274 Expression confers sensitivity to Atezolizumab in Bladder Urothelial Carcinoma (CIViC Level B); 13 further subtype–drug associations are mapped below. Top therapeutic interventions include pembrolizumab, cabozantinib, and eribulin mesylate.

At a glance

• Classification: Cancer
• Umbrella term: 5 Mondo subtypes
• Cohort genes: 8
• Clinical trials: 91
• Precision-medicine evidence (CIViC): 14 subtype–drug associations

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	bladder transitional cell carcinoma
Mondo ID	MONDO:0005611
EFO	EFO:0006544
DOID	DOID:4006
NCIT	C39851
SNOMED CT	255109008
UMLS	C0279680
MedGen	76013
Anatomy (UBERON)	UBERON:0001255
Is cancer (heuristic)	yes

Also known as: bladder transitional cell carcinoma · bladder urothelial cancer · bladder urothelial carcinoma · BLCA · transitional cell carcinoma of the urinary bladder · urinary bladder transitional cell carcinoma · urinary bladder urothelial carcinoma · urothelial carcinoma of the urinary bladder

Data availability: 15 cell lines · 93 intOGen driver records.

Disease family

An umbrella term covering 5 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › urinary system disorder › urinary bladder disorder › urinary bladder neoplasm › urinary bladder cancer › urinary bladder carcinoma › bladder transitional cell carcinoma

Related subtypes (8): bladder adenocarcinoma, bladder squamous cell carcinoma, bladder urachal carcinoma, urinary bladder small cell neuroendocrine carcinoma, stage IVb bladder cancer, superficial urinary bladder carcinoma, childhood bladder carcinoma, bladder small cell carcinoma

Subtypes (5): infiltrating bladder urothelial carcinoma, non-invasive bladder urothelial carcinoma, bladder papillary urothelial carcinoma, bladder urachal urothelial carcinoma, bladder sarcomatoid transitional 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: 50 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
TERT	Act	PRCC	CIViC #79
CD274	LoF	DLBCLNOS	CIViC #11335
CDKN2A	LoF	ACYC,BLCA,BRCA,CHOL,COAD,COADREAD,CSCC,EGC,ESCA,ESCC,GBM,HCC,HNSC,LGGNOS,LUAD,LUSC,MEL,MLYM,NPC,NSCLC,OS,PAAD,PANCREAS,RCC,SKCM,SKIN,STAD,STOMACH,WDTC	CIViC #14
ERBB2	Act	BLCA,BRCA,CESC,CHOL,COADREAD,EGC,ESCA,ESCC,LMS,LUAD,NSCLC,OVT,PRCC,READ,STAD,UCEC	CIViC #20
FGFR3	Act	BLADDER,BLCA,HNSC,LUSC,PCM,PLMESO,UTUC	CIViC #23
GNAS	Act	BRCA,COADREAD,ESCA,HCC,LUAD,MBL,PAAD,PANCREAS	CIViC #2319
HRAS	Act	ANGS,BLCA,BRCA,COADREAD,CSCC,HNSC,LUSC,NPC,PGNG,PRAD,PROSTATE,THYM,UTUC,WDTC	CIViC #2747
MTAP			CIViC #3659

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TERT	Orphanet:146	Differentiated thyroid carcinoma
TERT	Orphanet:1501	Adrenocortical carcinoma
TERT	Orphanet:1775	Dyskeratosis congenita
TERT	Orphanet:2032	Idiopathic pulmonary fibrosis
TERT	Orphanet:2495	Meningioma
TERT	Orphanet:3322	Hoyeraal-Hreidarsson syndrome
TERT	Orphanet:457246	Clear cell sarcoma of kidney
TERT	Orphanet:618	Familial melanoma
TERT	Orphanet:88	Idiopathic aplastic anemia
CDKN2A	Orphanet:1333	Familial pancreatic carcinoma
CDKN2A	Orphanet:1501	Adrenocortical carcinoma
CDKN2A	Orphanet:252206	Melanoma and neural system tumor syndrome
CDKN2A	Orphanet:404560	Familial atypical multiple mole melanoma syndrome
CDKN2A	Orphanet:524	Li-Fraumeni syndrome
CDKN2A	Orphanet:585909	B-lymphoblastic leukemia/lymphoma with t(9;22)(q34.1;q11.2)
CDKN2A	Orphanet:618	Familial melanoma
CDKN2A	Orphanet:99861	Precursor T-cell acute lymphoblastic leukemia
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
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
GNAS	Orphanet:189427	Cushing syndrome due to bilateral macronodular adrenocortical disease
GNAS	Orphanet:2762	Progressive osseous heteroplasia
GNAS	Orphanet:562	McCune-Albright syndrome
GNAS	Orphanet:57782	Mazabraud syndrome
GNAS	Orphanet:79443	Pseudohypoparathyroidism type 1A
GNAS	Orphanet:79444	Pseudohypoparathyroidism type 1C
GNAS	Orphanet:79445	Pseudopseudohypoparathyroidism
GNAS	Orphanet:93276	Polyostotic fibrous dysplasia
GNAS	Orphanet:93277	Monostotic fibrous dysplasia
GNAS	Orphanet:94089	Pseudohypoparathyroidism type 1B
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
MTAP	Orphanet:85182	Diaphyseal medullary stenosis-bone malignancy syndrome

Cohort genes → proteins

8 cohort genes, 8 distinct canonical proteins.

Evidence partition

Subset	Genes
civic_only	8

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TERT	HGNC:11730	ENSG00000164362	O14746	Telomerase reverse transcriptase	civic_evidence
CD274	HGNC:17635	ENSG00000120217	Q9NZQ7	Programmed cell death 1 ligand 1	civic_evidence
CDKN2A	HGNC:1787	ENSG00000147889	P42771	Cyclin-dependent kinase inhibitor 2A	civic_evidence
ERBB2	HGNC:3430	ENSG00000141736	P04626	Receptor tyrosine-protein kinase erbB-2	civic_evidence
FGFR3	HGNC:3690	ENSG00000068078	P22607	Fibroblast growth factor receptor 3	civic_evidence
GNAS	HGNC:4392	ENSG00000087460	O95467	Neuroendocrine secretory protein 55	civic_evidence
HRAS	HGNC:5173	ENSG00000174775	P01112	GTPase HRas	civic_evidence
MTAP	HGNC:7413	ENSG00000099810	Q13126	S-methyl-5’-thioadenosine phosphorylase	civic_evidence

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TERT	Telomerase reverse transcriptase	Telomerase is a ribonucleoprotein enzyme essential for the replication of chromosome termini in most eukaryotes.
CD274	Programmed cell death 1 ligand 1	Plays a critical role in induction and maintenance of immune tolerance to self.
CDKN2A	Cyclin-dependent kinase inhibitor 2A	Acts as a negative regulator of the proliferation of normal cells by interacting strongly with CDK4 and CDK6.
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.
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.
HRAS	GTPase HRas	Involved in the activation of Ras protein signal transduction.
MTAP	S-methyl-5’-thioadenosine phosphorylase	Catalyzes the reversible phosphorylation of S-methyl-5’-thioadenosine (MTA) to adenine and 5-methylthioribose-1-phosphate.

Protein-family classification

Druggable: 5 · Difficult: 1 · Unknown: 2 · Druggable fraction: 0.62

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	2	6.9×	0.157
Enzyme (other)	2	3.0×	0.348
Antibody/Immunoglobulin	1	3.6×	0.406
Scaffold/PPI	1	2.2×	0.474
Other/Unknown	2	0.5×	0.984

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TERT	Other/Unknown	no		RT_dom, Telomerase_RT, Telomerase_RBD
CD274	Antibody/Immunoglobulin	yes		Ig_sub, Ig-like_dom, Ig_V-set
CDKN2A	Scaffold/PPI	no		Ankyrin_rpt-contain_sf, Ank_Repeat/CDKN_Inhibitor, Tumor_suppres_ARF
ERBB2	Kinase	yes	2.7.10.1	Rcpt_L-dom, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom
FGFR3	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Ig_sub2
GNAS	Other/Unknown	no		NESP55, Gprotein_alpha_S, Gprotein_alpha_su
HRAS	Enzyme (other)	yes	3.6.5.2	Small_GTPase, Small_GTP-bd, Small_GTPase_Ras-type
MTAP	Enzyme (other)	yes	2.4.2.28	Nucleoside_phosphorylase_d, MTAP, Purine_phosphorylase-2_CS

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)	8
unknown	0

Top tissues across cohort

Tissue	Cohort genes
type B pancreatic cell	2
olfactory bulb	1
stromal cell of endometrium	1
cartilage tissue	1
lower lobe of lung	1
placenta	1
cervix squamous epithelium	1
parotid gland	1
pituitary gland	1
lower esophagus mucosa	1
right uterine tube	1
sural nerve	1
skin of hip	1
upper arm skin	1
upper leg skin	1
Brodmann (1909) area 46	1
postcentral gyrus	1
skin of abdomen	1
skin of leg	1
zone of skin	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TERT	105	broad	yes	stromal cell of endometrium, type B pancreatic cell, olfactory bulb
CD274	208	ubiquitous	marker	cartilage tissue, placenta, lower lobe of lung
CDKN2A	220	ubiquitous	marker	parotid gland, cervix squamous epithelium, pituitary gland
ERBB2	276	ubiquitous	marker	lower esophagus mucosa, right uterine tube, sural nerve
FGFR3	262	broad	marker	upper leg skin, skin of hip, upper arm skin
GNAS	312	ubiquitous	marker	type B pancreatic cell, postcentral gyrus, Brodmann (1909) area 46
HRAS	139	ubiquitous	marker	skin of abdomen, skin of leg, zone of skin
MTAP	239	ubiquitous	marker	adrenal tissue, calcaneal tendon, colonic epithelium

Protein interactions among cohort

Intra-cohort edges: 2.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ERBB2	9,659
CDKN2A	9,311
HRAS	8,064
TERT	5,717
CD274	5,012
FGFR3	4,510
MTAP	2,086
GNAS	410

Intra-cohort edges

A	B	Sources
CDKN2A	HRAS	string_interaction
CDKN2A	MTAP	string_interaction

Structural data

PDB: 8 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GNAS	O95467	490
HRAS	P01112	246
CD274	Q9NZQ7	76
ERBB2	P04626	63
TERT	O14746	23
MTAP	Q13126	18
FGFR3	P22607	15
CDKN2A	P42771	5

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 201. Enrichment computed across 8 evidence-associated genes (8 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 8 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Constitutive Signaling by Overexpressed ERBB2	2	237.9×	0.003	ERBB2, HRAS
Signaling by ERBB2 ECD mutants	2	167.9×	0.003	ERBB2, HRAS
GRB2 events in ERBB2 signaling	2	158.6×	0.003	ERBB2, HRAS
SHC-mediated cascade:FGFR3	2	150.3×	0.003	FGFR3, HRAS
FRS-mediated FGFR3 signaling	2	135.9×	0.003	FGFR3, HRAS
Signaling by FGFR3 in disease	2	124.1×	0.003	FGFR3, HRAS
SHC1 events in ERBB2 signaling	2	119.0×	0.003	ERBB2, HRAS
Signaling by ERBB2 TMD/JMD mutants	2	119.0×	0.003	ERBB2, HRAS
Signaling by ERBB2 KD Mutants	2	105.7×	0.003	ERBB2, HRAS
RAF/MAP kinase cascade	3	22.9×	0.005	ERBB2, FGFR3, HRAS
t(4;14) translocations of FGFR3	1	1427.5×	0.010	FGFR3
Signaling by FGFR3 fusions in cancer	1	1427.5×	0.010	FGFR3
Evasion of Oncogene Induced Senescence Due to p14ARF Defects	1	1427.5×	0.010	CDKN2A
Evasion of Oxidative Stress Induced Senescence Due to p14ARF Defects	1	1427.5×	0.010	CDKN2A
MITF-M-dependent gene expression	2	45.3×	0.011	TERT, CDKN2A
Evasion of Oncogene Induced Senescence Due to Defective p16INK4A binding to CDK4	1	713.8×	0.014	CDKN2A
Evasion of Oxidative Stress Induced Senescence Due to Defective p16INK4A binding to CDK4	1	713.8×	0.014	CDKN2A
Defective Intrinsic Pathway for Apoptosis Due to p14ARF Loss of Function	1	713.8×	0.014	CDKN2A
Diseases of Cellular Senescence	1	475.8×	0.014	CDKN2A
Evasion of Oncogene Induced Senescence Due to p16INK4A Defects	1	475.8×	0.014	CDKN2A
Evasion of Oncogene Induced Senescence Due to Defective p16INK4A binding to CDK4 and CDK6	1	475.8×	0.014	CDKN2A
Evasion of Oxidative Stress Induced Senescence Due to p16INK4A Defects	1	475.8×	0.014	CDKN2A
Evasion of Oxidative Stress Induced Senescence Due to Defective p16INK4A binding to CDK4 and CDK6	1	475.8×	0.014	CDKN2A
Diseases of cellular response to stress	1	475.8×	0.014	CDKN2A
Signaling by RAS GAP mutants	1	475.8×	0.014	HRAS
Signaling by RAS GTPase mutants	1	475.8×	0.014	HRAS
PLCG1 events in ERBB2 signaling	1	356.9×	0.014	ERBB2
Drug-mediated inhibition of ERBB2 signaling	1	356.9×	0.014	ERBB2
Resistance of ERBB2 KD mutants to trastuzumab	1	356.9×	0.014	ERBB2
Resistance of ERBB2 KD mutants to sapitinib	1	356.9×	0.014	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 8 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 immature T cell proliferation in thymus	2	702.2×	5e-04	CDKN2A, ERBB2
oncogene-induced cell senescence	2	601.9×	5e-04	CDKN2A, HRAS
Schwann cell development	2	263.3×	0.001	ERBB2, HRAS
replicative senescence	2	247.8×	0.001	TERT, CDKN2A
positive regulation of protein targeting to membrane	2	140.4×	0.004	ERBB2, HRAS
positive regulation of MAPK cascade	3	30.2×	0.004	ERBB2, FGFR3, HRAS
RNA-templated transcription	1	2106.5×	0.006	TERT
DNA strand elongation	1	2106.5×	0.006	TERT
negative regulation of developmental growth	1	2106.5×	0.006	FGFR3
siRNA transcription	1	2106.5×	0.006	TERT
negative regulation of tumor necrosis factor superfamily cytokine production	1	2106.5×	0.006	CD274
positive regulation of transdifferentiation	1	2106.5×	0.006	TERT
positive regulation of activated CD8-positive, alpha-beta T cell apoptotic process	1	2106.5×	0.006	CD274
cellular senescence	2	73.9×	0.006	CDKN2A, HRAS
myelination	2	62.9×	0.006	ERBB2, HRAS
positive regulation of epithelial cell proliferation	2	61.1×	0.006	ERBB2, HRAS
cell surface receptor signaling pathway	3	24.0×	0.006	CD274, ERBB2, HRAS
Ras protein signal transduction	2	51.4×	0.008	CDKN2A, HRAS
RNA-templated DNA biosynthetic process	1	1053.2×	0.010	TERT
nuclear body organization	1	1053.2×	0.010	CDKN2A
positive regulation of hair cycle	1	1053.2×	0.010	TERT
fibroblast growth factor receptor apoptotic signaling pathway	1	1053.2×	0.010	FGFR3
MAPK cascade	2	38.3×	0.011	FGFR3, HRAS
adenylate cyclase-activating G protein-coupled bile acid receptor signaling pathway	1	702.2×	0.011	GNAS
apoptotic process involved in mammary gland involution	1	702.2×	0.011	CDKN2A
bone maturation	1	702.2×	0.011	FGFR3
positive regulation of macrophage apoptotic process	1	702.2×	0.011	CDKN2A
positive regulation of miRNA metabolic process	1	702.2×	0.011	HRAS
positive regulation of apoptotic process involved in mammary gland involution	1	526.6×	0.013	CDKN2A
response to parathyroid hormone	1	526.6×	0.013	GNAS

Therapeutics

Drug target analysis

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

Druggability breadth: 8 of 8 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
TERT	BERBERINE
CD274	MOCLOBEMIDE
ERBB2	CLOTRIMAZOLE
FGFR3	PONATINIB
HRAS	LONAFARNIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ERBB2	83	4
FGFR3	64	4
TERT	10	4
CD274	4	4
HRAS	4	4
CDKN2A	0	0
GNAS	0	0
MTAP	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
BERBERINE	4	TERT
DOXORUBICIN	4	ERBB2, TERT
MOCLOBEMIDE	4	CD274
PYRVINIUM	4	CD274
RIFABUTIN	4	CD274
CLOTRIMAZOLE	4	ERBB2
ERLOTINIB HYDROCHLORIDE	4	ERBB2
PONATINIB	4	ERBB2, FGFR3
AFATINIB	4	ERBB2
LAPATINIB DITOSYLATE	4	ERBB2
SORAFENIB	4	ERBB2, FGFR3
NERATINIB	4	ERBB2
IBRUTINIB	4	ERBB2
AFATINIB DIMALEATE	4	ERBB2
CABOZANTINIB	4	ERBB2
DACOMITINIB	4	ERBB2
DACOMITINIB ANHYDROUS	4	ERBB2
VANDETANIB	4	ERBB2, FGFR3
TRIBROMSALAN	4	ERBB2
BOSUTINIB	4	ERBB2
BITHIONOL	4	ERBB2
ASTEMIZOLE	4	ERBB2
EBASTINE	4	ERBB2
OSIMERTINIB	4	ERBB2
BRIGATINIB	4	ERBB2, FGFR3
ACALABRUTINIB	4	ERBB2
ZANUBRUTINIB	4	ERBB2
TUCATINIB	4	ERBB2
TIRABRUTINIB	4	ERBB2
PACLITAXEL	4	ERBB2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 4.

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

Symbol	Assays	Type breakdown
ERBB2	1,221	Binding:1136, Functional:79, ADMET:6
FGFR3	975	Binding:948, Functional:18, ADMET:9
CD274	525	Binding:520, Functional:5
TERT	391	Binding:389, Functional:2
HRAS	48	Binding:45, Functional:3
MTAP	24	Binding:23, ADMET:1
CDKN2A	2	Binding:2

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ERBB2	2.7.10.1	receptor protein-tyrosine kinase
FGFR3	2.7.10.1	receptor protein-tyrosine kinase
HRAS	3.6.5.2	small monomeric GTPase
MTAP	2.4.2.28	S-methyl-5’-thioadenosine phosphorylase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
TERT	391
CD274	525
ERBB2	1,221
FGFR3	975

Pharmacogenomics

Cohort genes with a PharmGKB record: 8; 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)
BERBERINE	4	TERT
DOXORUBICIN	4	ERBB2, TERT
MOCLOBEMIDE	4	CD274
PYRVINIUM	4	CD274
RIFABUTIN	4	CD274
CLOTRIMAZOLE	4	ERBB2
ERLOTINIB HYDROCHLORIDE	4	ERBB2
PONATINIB	4	ERBB2, FGFR3
AFATINIB	4	ERBB2
LAPATINIB DITOSYLATE	4	ERBB2
SORAFENIB	4	ERBB2, FGFR3
NERATINIB	4	ERBB2
IBRUTINIB	4	ERBB2
AFATINIB DIMALEATE	4	ERBB2
DACOMITINIB	4	ERBB2
DACOMITINIB ANHYDROUS	4	ERBB2
VANDETANIB	4	ERBB2, FGFR3
TRIBROMSALAN	4	ERBB2
BOSUTINIB	4	ERBB2
BITHIONOL	4	ERBB2
ASTEMIZOLE	4	ERBB2
EBASTINE	4	ERBB2
OSIMERTINIB	4	ERBB2
BRIGATINIB	4	ERBB2, FGFR3
ACALABRUTINIB	4	ERBB2
ZANUBRUTINIB	4	ERBB2
TUCATINIB	4	ERBB2
TIRABRUTINIB	4	ERBB2
PACLITAXEL	4	ERBB2

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	5	TERT, CD274, ERBB2, FGFR3, HRAS
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	MTAP
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	CDKN2A, GNAS

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
CDKN2A	2	—
GNAS	0	—
MTAP	24	—

Clinical trials & evidence

Clinical trials

Clinical trials: 91.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	32
Not specified	24
PHASE1	17
PHASE3	8
PHASE1/PHASE2	4
EARLY_PHASE1	3
PHASE4	2
PHASE2/PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06764095	PHASE4	RECRUITING	Enfortumab Vedotin and Pembrolizumab With Cystectomy and/or Ureterectomy for Locally Advanced or Metastatic Bladder and Upper Urothelial Tract Cancer, CAST-AI Trial
NCT05220124	PHASE4	UNKNOWN	A Study of Probiotics Administration in the Immunotherapy of Urothelial Bladder Carcinoma
NCT03091660	PHASE3	ACTIVE_NOT_RECRUITING	S1602: Different Strains of BCG With or Without Vaccine in High Grade Non- Muscle Invasive Bladder Cancer
NCT03244384	PHASE3	ACTIVE_NOT_RECRUITING	Testing MK-3475 (Pembrolizumab) After Surgery for Localized Muscle-Invasive Bladder Cancer and Locally Advanced Urothelial Cancer
NCT03775265	PHASE3	ACTIVE_NOT_RECRUITING	Chemoradiotherapy With or Without Atezolizumab in Treating Patients With Localized Muscle Invasive Bladder Cancer
NCT04574960	PHASE3	RECRUITING	Neoadjuvant Upper Tract Invasive Cancer Trial (NAUTICAL)
NCT04579224	PHASE3	ACTIVE_NOT_RECRUITING	Comparing the New Anti-cancer Drug Eribulin With Chemotherapy Against the Usual Chemotherapy Alone in Metastatic Urothelial Cancer
NCT04637594	PHASE3	ACTIVE_NOT_RECRUITING	Trying to Find the Correct Length of Treatment With Immune Checkpoint Therapy
NCT05092958	PHASE3	ACTIVE_NOT_RECRUITING	Testing the Addition of the Anti-cancer Drug, Cabozantinib, to the Usual Immunotherapy Treatment, Avelumab, in Patients With Metastatic Urothelial Cancer, MAIN-CAV Study
NCT05987241	PHASE2/PHASE3	RECRUITING	Testing the Role of DNA Released From Tumor Cells Into the Blood in Guiding the Use of Immunotherapy After Surgical Removal of the Bladder, Kidney, Ureter, and Urethra for Urothelial Cancer Treatment, MODERN Study
NCT00942331	PHASE3	COMPLETED	Gemcitabine Hydrochloride and Cisplatin With or Without Bevacizumab in Treating Patients With Advanced Urinary Tract Cancer
NCT00365157	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Eribulin Mesylate in Treating Patients With Locally Advanced or Metastatic Cancer of the Urothelium and Kidney Dysfunction
NCT02202772	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Intravesical Cabazitaxel, Gemcitabine, and Cisplatin (CGC) in the Treatment Urothelial Carcinoma of the Bladder
NCT02717156	PHASE2	ACTIVE_NOT_RECRUITING	Multicohort Phase II Trial of sEphB4-HSA+Pembrolizumab in Solid Tumors
NCT03047213	PHASE2	ACTIVE_NOT_RECRUITING	Sapanisertib in Treating Patients With Locally Advanced or Metastatic Bladder Cancer With TSC1 and/or TSC2 Mutations
NCT03237780	PHASE2	ACTIVE_NOT_RECRUITING	Atezolizumab With or Without Eribulin Mesylate in Treating Patients With Recurrent Locally Advanced or Metastatic Urothelial Cancer
NCT03601455	PHASE2	ACTIVE_NOT_RECRUITING	Radiation Therapy and Durvalumab With or Without Tremelimumab in Treating Participants With Unresectable, Locally Advanced, or Metastatic Bladder Cancer
NCT03609216	PHASE2	ACTIVE_NOT_RECRUITING	Gemcitabine and Cisplatin Without Cystectomy for Patients With Muscle Invasive Bladder Urothelial Cancer and Select Genetic Alterations
NCT04216290	PHASE2	ACTIVE_NOT_RECRUITING	A Study of Chemotherapy and Radiation Therapy Compared to Chemotherapy and Radiation Therapy Plus MEDI4736 (Durvalumab) Immunotherapy for Bladder Cancer Which Has Spread to the Lymph Nodes, INSPIRE Trial
NCT04848519	PHASE2	ACTIVE_NOT_RECRUITING	Immune Checkpoint Inhibitors With or Without Propranolol Hydrochloride In Patients With Urothelial Carcinoma
NCT04940299	PHASE2	ACTIVE_NOT_RECRUITING	Tocilizumab, Ipilimumab, and Nivolumab for the Treatment of Advanced Melanoma, Non-Small Cell Lung Cancer, or Urothelial Carcinoma
NCT04953104	PHASE2	ACTIVE_NOT_RECRUITING	ARID1A and/or KDM6A Mutation and CXCL13 Expression
NCT05296564	PHASE1/PHASE2	RECRUITING	Anti-NY-ESO-1 TCR-Gene Engineered Lymphocytes Given by Infusion to Patients With NY-ESO-1 -Expressing Metastatic Cancers
NCT06263153	PHASE2	RECRUITING	Futibatinib in Combination With Durvalumab Prior to Cystectomy for the Treatment of Muscle-Invasive Bladder Cancer Patients Who Are Ineligible for Cisplatin-based Therapy
NCT06528483	PHASE2	NOT_YET_RECRUITING	Bladder Preservation With Sacituzumab Govitecan + Zimberelimab for Muscle-Invasive Bladder Cancer
NCT06630416	PHASE2	RECRUITING	Pemetrexed Response in Relation to Tumor Alterations of Gene Status for the Treatment of Patients With Metastatic Urothelial Bladder Cancer and Other Solid Tumors
NCT07087860	PHASE2	RECRUITING	Therapeutic Plasma Exchange With Enfortumab Vedotin and Pembrolizumab for Treatment of Bladder Cancers
NCT07414992	PHASE2	NOT_YET_RECRUITING	A Study of Radiation Therapy and Cemiplimab With or Without Fianlimab In People With Bladder Cancer
NCT00238420	PHASE1/PHASE2	COMPLETED	Paclitaxel and Radiation Therapy With or Without Trastuzumab in Treating Patients Who Have Undergone Surgery for Bladder Cancer
NCT00749892	PHASE2	COMPLETED	Erlotinib Hydrochloride in Treating Participants With Muscle Invasive or Recurrent Urothelial Cancer
NCT01599013	PHASE2	COMPLETED	JAVLOR Association Study in CDDP-unfit Patients With Advanced Transitional Cell Carcinoma: Gemcitabine Versus Carboplatin
NCT02178241	PHASE2	COMPLETED	Gemcitabine Hydrochloride and Eribulin Mesylate in Treating Patients With Bladder Cancer That is Advanced or Cannot Be Removed by Surgery
NCT02567409	PHASE2	COMPLETED	Cisplatin and Gemcitabine Hydrochloride With or Without Berzosertib in Treating Patients With Metastatic Urothelial Cancer
NCT02718742	PHASE2	WITHDRAWN	Paclitaxel Albumin-Stabilized Nanoparticle Formulation After Cisplatin-Based Chemotherapy and Surgery in Treating Patients With High-Risk Bladder Cancer
NCT02844816	PHASE2	COMPLETED	Atezolizumab in Treating Patients With Recurrent BCG-Unresponsive Non-muscle Invasive Bladder Cancer
NCT03113266	PHASE2	UNKNOWN	Safety and Efficacy of Toripalimab for Patients With Locally Advanced or Metastatic Bladder Urothelial Carcinoma
NCT03421652	PHASE2	COMPLETED	Nivolumab and RT in Treating Patients With Localized/Locally Advanced Urothelial Bladder Cancer Ineligible for Chemo
NCT03513952	PHASE2	COMPLETED	Atezolizumab and CYT107 in Treating Participants With Locally Advanced, Inoperable, or Metastatic Urothelial Carcinoma
NCT03912818	PHASE2	TERMINATED	Durvalumab and Standard Chemotherapy Before Surgery in Treating Patients With Variant Histology Bladder Cancer
NCT03935347	PHASE2	WITHDRAWN	Adoptive Cell Therapy With (LN-145) in Combination With Pembrolizumab in Treating Patients With Unresectable or Metastatic Transitional Cell Cancer Who Have Failed Cisplatin-Based Chemotherapy

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
PEMBROLIZUMAB	4	10
CABOZANTINIB	4	4
ERIBULIN MESYLATE	4	4
ENFORTUMAB VEDOTIN	4	3
ERDAFITINIB	4	3
ATEZOLIZUMAB	4	2
AVELUMAB	4	2
GEMCITABINE	4	2
RELATLIMAB	4	2
SACITUZUMAB GOVITECAN	4	2
TISLELIZUMAB	4	2
CABAZITAXEL	4	1
DURVALUMAB	4	1
FUTIBATINIB	4	1
INFIGRATINIB	4	1
LIFILEUCEL	4	1
MITOMYCIN	4	1
TOVORAFENIB	4	1
VINBLASTINE	4	1
VINFLUNINE	4	1
FIANLIMAB	3	1
MILADEMETAN	3	1
ZIMBERELIMAB	3	1
SEPHB4-HSA	2	2
BERZOSERTIB	2	1
CDX-1140	2	1
CDX-301	2	1
SAPANISERTIB	2	1
CHEMBL5412235	0	2
CHEMBL3962632	0	1

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 14 predictive associations from 14 curated evidence items; also 7 oncogenic, 4 prognostic, 2 predisposing, 1 diagnostic.

Molecular subtype	Therapy	Effect	Level	CIViC
CD274 Expression	Atezolizumab	Sensitivity/Response	CIViC B	EID9886
FGFR3 Mutation	Erdafitinib	Sensitivity/Response	CIViC B	EID10397
HRAS Mutation	Tipifarnib	Sensitivity/Response	CIViC B	EID9632
MTAP Deletion	Pemetrexed	Sensitivity/Response	CIViC B	EID12722
CDKN2A Loss	Immune Checkpoint Inhibitor	Resistance	CIViC B	EID12546
FGFR2::? Fusion	Erdafitinib	Sensitivity/Response	CIViC C	EID10404
FGFR3::v Fusion	Erdafitinib	Sensitivity/Response	CIViC C	EID10405
ERBB2 D277H	Lapatinib	Sensitivity/Response	CIViC D	EID11363
ERBB2 L15F	Lapatinib	Sensitivity/Response	CIViC D	EID11231
ERBB2 R143Q	Lapatinib	Sensitivity/Response	CIViC D	EID11361
ERBB2 R678Q	Lapatinib	Sensitivity/Response	CIViC D	EID11470
ERBB2 S310F	Lapatinib	Sensitivity/Response	CIViC D	EID11365
ERBB2 S653C	Lapatinib	Sensitivity/Response	CIViC D	EID11468
FGFR3 S249C	Erdafitinib	Sensitivity/Response	CIViC D	EID12954