Mesothelioma

Summary

Mesothelioma (MONDO:0005065) is a disease (an umbrella term covering 7 Mondo subtypes) with 2 cohort genes and 217 clinical trials. Top therapeutic interventions include pemetrexed, tazemetostat, and ipilimumab.

At a glance

• Umbrella term: 7 Mondo subtypes
• Cohort genes: 2
• ClinVar variants: 3
• Clinical trials: 217

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	mesothelioma
Mondo ID	MONDO:0005065
EFO	EFO:0000588
MeSH	D008654
ICD-10-CM	C45
NCIT	C3234
UMLS	C0025500
MedGen	9975
Is cancer (heuristic)	no

Also known as: mesothelioma

Data availability: 3 ClinVar variants.

Disease family

An umbrella term covering 7 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › mesothelial neoplasm › mesothelioma

Subtypes (7): benign mesothelioma, pleural mesothelioma, well differentiated papillary mesothelioma, adenomatoid tumor, malignant mesothelioma, peritoneal mesothelioma, well-differentiated papillary mesothelial tumour of the pleura

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

3 retrieved; paginated sample, class counts are floors:

3 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
6250	NM_003921.5(BCL10):c.499dup (p.Ser167fs)	BCL10	Pathogenic	no assertion criteria provided
6263	NM_003921.5(BCL10):c.136del (p.Ile46fs)	BCL10	Pathogenic	no assertion criteria provided
3499	NM_024426.6(WT1):c.1036A>G (p.Ser346Gly)	WT1	Pathogenic	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 10 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
WT1	Orphanet:220	Denys-Drash syndrome
WT1	Orphanet:242	46,XY complete gonadal dysgenesis
WT1	Orphanet:251510	46,XY partial gonadal dysgenesis
WT1	Orphanet:3097	Meacham syndrome
WT1	Orphanet:347	Frasier syndrome
WT1	Orphanet:654	Nephroblastoma
WT1	Orphanet:656	Hereditary steroid-resistant nephrotic syndrome
WT1	Orphanet:83469	Desmoplastic small round cell tumor
WT1	Orphanet:893	WAGR syndrome
BCL10	Orphanet:52417	MALT lymphoma

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
WT1	HGNC:12796	ENSG00000184937	P19544	Wilms tumor protein	clinvar
BCL10	HGNC:989	ENSG00000142867	O95999	B-cell lymphoma/leukemia 10	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
WT1	Wilms tumor protein	Transcription factor that plays an important role in cellular development and cell survival.
BCL10	B-cell lymphoma/leukemia 10	Plays a key role in both adaptive and innate immune signaling by bridging CARD domain-containing proteins to immune activation.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 1 · Druggable fraction: 0.0

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
Transcription factor	1	4.1×	0.455
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
WT1	Transcription factor	no		Wilms_tumour_N, Znf_C2H2_type, Znf_C2H2_sf
BCL10	Other/Unknown	no		CARD, DEATH-like_dom_sf, BCL10/E10

Expression context

Cohort genes with no expression data: 0.

2 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
germinal epithelium of ovary	1
metanephric glomerulus	1
renal glomerulus	1
esophagus squamous epithelium	1
mucosa of sigmoid colon	1
squamous epithelium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
WT1	168	broad	marker	germinal epithelium of ovary, renal glomerulus, metanephric glomerulus
BCL10	280	ubiquitous	marker	esophagus squamous epithelium, mucosa of sigmoid colon, squamous epithelium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
WT1	3,938
BCL10	1,873

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
WT1	P19544	28
BCL10	O95999	5

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 19. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Nephron development	1	439.2×	0.013	WT1
Downstream signaling events of B Cell Receptor (BCR)	1	407.9×	0.013	BCL10
Protein ubiquitination	1	407.9×	0.013	BCL10
Transcriptional regulation of testis differentiation	1	356.9×	0.013	WT1
TCR signaling	1	248.3×	0.015	BCL10
Signaling by the B Cell Receptor (BCR)	1	173.0×	0.018	BCL10
Fc epsilon receptor (FCERI) signaling	1	135.9×	0.020	BCL10
C-type lectin receptors (CLRs)	1	119.0×	0.020	BCL10
Activation of NF-kappaB in B cells	1	98.5×	0.020	BCL10
E3 ubiquitin ligases ubiquitinate target proteins	1	96.8×	0.020	BCL10
FCERI mediated NF-kB activation	1	78.2×	0.022	BCL10
CLEC7A (Dectin-1) signaling	1	71.4×	0.022	BCL10
Downstream TCR signaling	1	64.2×	0.022	BCL10
Negative Regulation of CDH1 Gene Transcription	1	60.1×	0.022	WT1
Adaptive Immune System	1	14.9×	0.084	BCL10
Innate Immune System	1	12.8×	0.091	BCL10
Post-translational protein modification	1	9.6×	0.113	BCL10
Immune System	1	6.5×	0.155	BCL10
Metabolism of proteins	1	6.2×	0.155	BCL10

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 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 metanephric glomerular mesangial cell proliferation	1	8426.0×	0.003	WT1
regulation of animal organ formation	1	4213.0×	0.003	WT1
adrenal cortex formation	1	4213.0×	0.003	WT1
visceral serous pericardium development	1	4213.0×	0.003	WT1
posterior mesonephric tubule development	1	4213.0×	0.003	WT1
positive regulation of metanephric ureteric bud development	1	4213.0×	0.003	WT1
positive regulation of lymphotoxin A production	1	2808.7×	0.003	BCL10
negative regulation of mature B cell apoptotic process	1	2106.5×	0.003	BCL10
positive regulation of heart growth	1	2106.5×	0.003	WT1
metanephric S-shaped body morphogenesis	1	2106.5×	0.003	WT1
negative regulation of female gonad development	1	2106.5×	0.003	WT1
thorax and anterior abdomen determination	1	1685.2×	0.003	WT1
positive regulation of mast cell cytokine production	1	1685.2×	0.003	BCL10
cardiac muscle cell fate commitment	1	1685.2×	0.003	WT1
metanephric epithelium development	1	1685.2×	0.003	WT1
positive regulation of apoptotic process	2	56.7×	0.003	WT1, BCL10
cellular response to gonadotropin stimulus	1	1404.3×	0.003	WT1
metanephric mesenchyme development	1	1203.7×	0.004	WT1
tissue development	1	936.2×	0.004	WT1
diaphragm development	1	936.2×	0.004	WT1
sex determination	1	842.6×	0.004	WT1
positive regulation of male gonad development	1	842.6×	0.004	WT1
quinolinate biosynthetic process	1	766.0×	0.004	BCL10
glomerular basement membrane development	1	766.0×	0.004	WT1
mesenchymal to epithelial transition	1	766.0×	0.004	WT1
B cell apoptotic process	1	702.2×	0.004	BCL10
podocyte differentiation	1	702.2×	0.004	WT1
programmed cell death	1	648.1×	0.004	BCL10
glomerulus development	1	648.1×	0.004	WT1
T cell apoptotic process	1	648.1×	0.004	BCL10

Therapeutics

Drugs indicated for this disease

2 approved, 14 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Nivolumab	Approved (phase 4)
Pemetrexed	Approved (phase 4)
Atezolizumab	Phase 3 (in late-stage trials)
Bevacizumab	Phase 3 (in late-stage trials)
Carboplatin	Phase 3 (in late-stage trials)
Cisplatin	Phase 3 (in late-stage trials)
Durvalumab	Phase 3 (in late-stage trials)
Gemcitabine	Phase 3 (in late-stage trials)
Ipilimumab	Phase 3 (in late-stage trials)
Mitomycin	Phase 3 (in late-stage trials)
Pembrolizumab	Phase 3 (in late-stage trials)
Raltitrexed	Phase 3 (in late-stage trials)
Ranpirnase	Phase 3 (in late-stage trials)
Vinorelbine	Phase 3 (in late-stage trials)
Volrustomig	Phase 3 (in late-stage trials)
Vorinostat	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): ANTINEOPLASTON A10, Abemaciclib, Belinostat, Bintrafusp Alfa, Bortezomib, Cadonilimab, Capecitabine, Catequentinib, Cyanocobalamin, Dasatinib Anhydrous, Dexamethasone, Dostarlimab, Doxorubicin, Erlotinib, Everolimus, Folic Acid, Gefitinib, INTERFERON GAMMA-1B, Lenvatinib, Lurbinectedin, Magnesium Sulfate Anhydrous, Methotrexate, Nintedanib, Niraparib, Olaparib, Oxaliplatin, Pegargiminase, Porfimer Sodium, Ramucirumab, Rilotumumab, Rucaparib, Sacituzumab Govitecan, Semaxanib, Sintilimab, Sodium Chloride, Sorafenib, Tazemetostat, Tivantinib, Trabectedin, Tremelimumab, Vandetanib, Vatalanib.

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
WT1	0	0
BCL10	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
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	2	WT1, BCL10

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
WT1	0	—
BCL10	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 217.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE1	58
PHASE2	57
Not specified	52
PHASE1/PHASE2	29
PHASE3	7
PHASE2/PHASE3	5
EARLY_PHASE1	5
PHASE4	4

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03655821	PHASE4	TERMINATED	Dose Individualization of Pemetrexed - IMPROVE-II
NCT03655834	PHASE4	COMPLETED	Dose Individualization of Pemetrexed - IMPROVE-III
NCT03656549	PHASE4	COMPLETED	Dose Individualization of Pemetrexed - IMPROVE-I
NCT06010277	PHASE4	UNKNOWN	Folinic Acid for Prevention of Pemetrexed-induced Toxicity
NCT00128102	PHASE3	COMPLETED	Suberoylanilide Hydroxamic Acid (Vorinostat, MK-0683) Versus Placebo in Advanced Malignant Pleural Mesothelioma (MK-0683-014)
NCT00190762	PHASE3	COMPLETED	A Study Comparing Pemetrexed Plus Best Supportive Care Versus Best Supportive Care Alone in the Treatment of Mesothelioma
NCT00651456	PHASE2/PHASE3	COMPLETED	Mesothelioma Avastin Plus Pemetrexed-cisplatin Study
NCT01604005	PHASE3	TERMINATED	PIT: Prophylactic Irradiation of Tracts in Patients With Malignant Pleural Mesothelioma
NCT01907100	PHASE2/PHASE3	TERMINATED	Nintedanib (BIBF 1120) in Mesothelioma
NCT02511600	PHASE3	WITHDRAWN	Comparison of Progel Sealant to Standard of Care (SOC) for Patients Undergoing Decortication
NCT02709512	PHASE2/PHASE3	COMPLETED	Ph 2/3 Study in Subjects With MPM to Assess ADI-PEG 20 With Pemetrexed and Cisplatin
NCT02784171	PHASE2/PHASE3	COMPLETED	Pembrolizumab in Patients With Advanced Malignant Pleural Mesothelioma
NCT02899299	PHASE3	COMPLETED	Study of Nivolumab Combined With Ipilimumab Versus Pemetrexed and Cisplatin or Carboplatin as First Line Therapy in Unresectable Pleural Mesothelioma Patients
NCT03063450	PHASE3	COMPLETED	CheckpOiNt Blockade For Inhibition of Relapsed Mesothelioma
NCT03610360	PHASE2/PHASE3	COMPLETED	DENdritic Cell Immunotherapy for Mesothelioma
NCT04334759	PHASE3	COMPLETED	DuRvalumab With chEmotherapy as First Line treAtment in Advanced Pleural Mesothelioma
NCT00715611	PHASE2	ACTIVE_NOT_RECRUITING	Pleurectomy/Decortication (Neo) Adjuvant Chemotherapy and Intensity Modulated Radiation Therapy to the Pleura in Patients With Locally Advanced Malignant Pleural Mesothelioma
NCT02414269	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Malignant Pleural Disease Treated With Autologous T Cells Genetically Engineered to Target the Cancer-Cell Surface Antigen Mesothelin
NCT02628067	PHASE2	ACTIVE_NOT_RECRUITING	Study of Pembrolizumab (MK-3475) in Participants With Advanced Solid Tumors (MK-3475-158/KEYNOTE-158)
NCT03556228	PHASE1/PHASE2	RECRUITING	VMD-928 Monotherapy and in Combination With Pembrolizumab to Treat TrkA Overexpression Driven Solid Tumors or Lymphoma
NCT03907852	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Phase 1/2 Trial of Gavo-cel (TC-210) in Patients With Advanced Mesothelin-Expressing Cancer
NCT03918252	PHASE2	ACTIVE_NOT_RECRUITING	Neoadjuvant Immune Checkpoint Blockade in Resectable Malignant Pleural Mesothelioma
NCT03935893	PHASE2	RECRUITING	Adoptive Transfer of Tumor Infiltrating Lymphocytes for Advanced Solid Cancers
NCT04300244	PHASE2	ACTIVE_NOT_RECRUITING	Nivolumab and Ipilimumab +/- UV1 Vaccination as Second Line Treatment in Patients With Malignant Mesothelioma
NCT04515836	PHASE2	RECRUITING	Olaparib in Patients With HRD Malignant Mesothelioma
NCT04665206	PHASE1/PHASE2	RECRUITING	Study to Evaluate VT3989 in Patients With Metastatic Solid Tumors
NCT04802876	PHASE2	ACTIVE_NOT_RECRUITING	Efficacy of Tislelizumab and Spartalizumab Across Multiple Cancer-types in Patients with PD1-high MRNA Expressing Tumors
NCT04913337	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Study of NGM707 As Monotherapy and in Combination with Pembrolizumab in Advanced or Metastatic Solid Tumor Malignancies
NCT05451849	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Phase 1/2 Trial of TC-510 In Patients With Advanced Mesothelin-Expressing Cancer
NCT05579366	PHASE1/PHASE2	RECRUITING	Rinatabart Sesutecan (Rina-S, PRO1184, GEN1184) for Advanced Solid Tumors (GCT1184-01/ PRO1184-001)
NCT05703854	PHASE1/PHASE2	RECRUITING	Study of CAR.70-engineered IL15-transduced Cord Blood-derived NK Cells in Conjunction With Lymphodepleting Chemotherapy for the Management of Advanced Renal Cell Carcinoma, Mesothelioma and Osteosarcoma
NCT05730816	PHASE2	RECRUITING	MAGIC AKI: Magnesium for the Prevention of HIOC-Associated AKI
NCT05932199	PHASE1/PHASE2	RECRUITING	Neoadjuvant Durvalumab and Tremelimumab With and Without Chemotherapy for Mesothelioma
NCT06051695	PHASE1/PHASE2	RECRUITING	A Study to Evaluate the Safety and Efficacy of Mesothelin-Targeting Logic-gated CAR T, in Participants With Solid Tumors That Express MSLN and Have Lost HLA-A*02 Expression
NCT06057935	PHASE2	RECRUITING	A Study of Additional Chemotherapy After Surgery for People With Malignant Peritoneal Mesothelioma
NCT06477419	PHASE2	RECRUITING	A Study of Sacituzumab Govitecan in People With Mesothelioma
NCT06503146	PHASE2	RECRUITING	18F-Fibroblast Activation Protein Inhibitor ([18F]FAPI-74) PET Imaging for Cancer Detection
NCT06638931	PHASE2	RECRUITING	Agnostic Therapy in Rare Solid Tumors
NCT06710756	PHASE1/PHASE2	RECRUITING	Lead-212 PSV359 Therapy for Patients With Solid Tumors
NCT07131345	PHASE1/PHASE2	NOT_YET_RECRUITING	Study of Iparomlimab and Tuvonralimab Plus Chemotherapy in Malignant Mesothelioma

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
PEMETREXED	4	32
TAZEMETOSTAT	4	3
IPILIMUMAB	4	2
IRINOTECAN HYDROCHLORIDE	4	2
NIRAPARIB	4	2
NIVOLUMAB	4	2
PLICAMYCIN	4	2
TREMELIMUMAB	4	2
BOSUTINIB	4	1
CEDAZURIDINE	4	1
CYANOCOBALAMIN	4	1
DOSTARLIMAB	4	1
DOXEPIN HYDROCHLORIDE	4	1
DURVALUMAB	4	1
ERLOTINIB	4	1
FAMOTIDINE	4	1
FLUDEOXYGLUCOSE F 18	4	1
IODIXANOL	4	1
IOHEXOL	4	1
IOPAMIDOL	4	1
LEUCOVORIN	4	1
LURBINECTEDIN	4	1
MITOMYCIN	4	1
NINTEDANIB	4	1
PANOBINOSTAT	4	1
PEMBROLIZUMAB	4	1
PENTOSTATIN	4	1
RAMUCIRUMAB	4	1
ROMIDEPSIN	4	1
SACITUZUMAB GOVITECAN	4	1