Malignant peritoneal mesothelioma

Summary

Malignant peritoneal mesothelioma (MONDO:0005512) is a disease with 3 cohort genes and 6 clinical trials. Top therapeutic interventions include erlotinib hydrochloride, interferon alfa-2b, and rintatolimod.

At a glance

• Prevalence: 1-9 / 100 000 (Europe) [Orphanet-validated]
• Cohort genes: 3
• ClinVar variants: 3
• Phenotypes (HPO): 10
• Clinical trials: 6

Clinical features

Epidemiology

Prevalence records

3 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 100 000		Europe	Validated
Annual incidence	1-9 / 1 000 000	0.2	France	Validated
Annual incidence	1-9 / 1 000 000	0.5	Italy	Validated

Signs & symptoms

Clinical features (HPO)

10 HPO clinical features (Orphanet curated; top 10 by frequency):

HPO ID	Term	Frequency
HP:0001541	Ascites	Very frequent (80-99%)
HP:0002027	Abdominal pain	Very frequent (80-99%)
HP:0002586	Peritonitis	Very frequent (80-99%)
HP:0002664	Neoplasm	Very frequent (80-99%)
HP:0003270	Abdominal distention	Very frequent (80-99%)
HP:0001824	Weight loss	Frequent (30-79%)
HP:0001928	Abnormality of coagulation	Occasional (5-29%)
HP:0002094	Dyspnea	Occasional (5-29%)
HP:0002595	Ileus	Occasional (5-29%)
HP:0010741	Pedal edema	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	malignant peritoneal mesothelioma
Mondo ID	MONDO:0005512
EFO	EFO:0005567
Orphanet	168811
DOID	DOID:1788
NCIT	C8704
UMLS	C0346109
MedGen	83406
GARD	0020102
MedDRA	10056558
Anatomy (UBERON)	UBERON:0002358
Is cancer (heuristic)	no

Also known as: advanced malignant mesothelioma of peritoneum · advanced malignant mesothelioma of the peritoneum · advanced peritoneal malignant mesothelioma · diffuse malignant peritoneal mesothelioma · malignant mesothelioma (disease) of peritoneum · malignant peritoneal mesothelioma, advanced · peritoneal mesothelioma (disease), malignant · peritoneum malignant mesothelioma (disease) · primary malignant peritoneal mesothelioma

Data availability: 3 ClinVar variants · 13 cell lines.

Disease family

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

Related subtypes (5): round ligament malignant neoplasm, peritoneal carcinoma, malignant peritoneal solitary fibrous tumor, malignant peritoneal germ cell tumor, peritoneal carcinomatosis

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:

2 likely pathogenic, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
619199	NM_004690.4(LATS1):c.2636G>A (p.Trp879Ter)	LATS1	Likely pathogenic	no assertion criteria provided
619198	NM_014572.3(LATS2):c.2699_2700insC (p.Val901fs)	LATS2	Likely pathogenic	no assertion criteria provided
619200	NM_004991.4(MECOM):c.262C>T (p.Pro88Ser)	MECOM	Uncertain significance	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MECOM	Orphanet:402020	Acute myeloid leukemia with inv(3)(q21q26.2) or t(3;3)(q21;q26.2)
MECOM	Orphanet:71289	Radio-ulnar synostosis-amegakaryocytic thrombocytopenia syndrome

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
MECOM	HGNC:3498	ENSG00000085276	Q03112	Histone-lysine N-methyltransferase MECOM	clinvar
LATS1	HGNC:6514	ENSG00000131023	O95835	Serine/threonine-protein kinase LATS1	clinvar
LATS2	HGNC:6515	ENSG00000150457	Q9NRM7	Serine/threonine-protein kinase LATS2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MECOM	Histone-lysine N-methyltransferase MECOM	Functions as a transcriptional regulator binding to DNA sequences in the promoter region of target genes and regulating positively or negatively their expression.
LATS1	Serine/threonine-protein kinase LATS1	Negative regulator of YAP1 in the Hippo signaling pathway that plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis.
LATS2	Serine/threonine-protein kinase LATS2	Negative regulator of YAP1 in the Hippo signaling pathway that plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis.

Protein-family classification

Druggable: 2 · Difficult: 1 · Unknown: 0 · Druggable fraction: 0.67

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	18.5×	0.008
Transcription factor	1	2.8×	0.321

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MECOM	Transcription factor	no		SET_dom, Znf_C2H2_type, Znf_C2H2_sf
LATS1	Kinase	yes		Prot_kinase_dom, AGC-kinase_C, Ser/Thr_kinase_AS
LATS2	Kinase	yes		Prot_kinase_dom, AGC-kinase_C, Ser/Thr_kinase_AS

Expression context

Cohort genes with no expression data: 0.

3 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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cardia of stomach	1
pylorus	1
renal medulla	1
germinal epithelium of ovary	1
mucosa of paranasal sinus	1
tibia	1
epithelial cell of pancreas	1
left ventricle myocardium	1
visceral pleura	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MECOM	276	ubiquitous	marker	cardia of stomach, renal medulla, pylorus
LATS1	263	ubiquitous	marker	germinal epithelium of ovary, tibia, mucosa of paranasal sinus
LATS2	255	ubiquitous	marker	epithelial cell of pancreas, left ventricle myocardium, visceral pleura

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
LATS1	2,732
MECOM	2,442
LATS2	2,063

Intra-cohort edges

A	B	Sources
LATS1	LATS2	intact

Structural data

PDB: 3 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
LATS1	O95835	4
MECOM	Q03112	1
LATS2	Q9NRM7	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 12. Enrichment computed across 3 evidence-associated genes (3 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 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Signaling by Hippo	2	362.5×	1e-04	LATS1, LATS2
Signal Transduction	3	10.2×	0.006	MECOM, LATS1, LATS2
Kidney development	1	271.9×	0.014	MECOM
Formation of the nephric duct	1	211.5×	0.014	MECOM
PTEN Regulation	1	76.1×	0.031	MECOM
Regulation of PTEN gene transcription	1	59.5×	0.032	MECOM
PKMTs methylate histone lysines	1	53.6×	0.032	MECOM
Intracellular signaling by second messengers	1	30.4×	0.048	MECOM
Chromatin organization	1	27.2×	0.048	MECOM
Chromatin modifying enzymes	1	24.1×	0.048	MECOM
PIP3 activates AKT signaling	1	22.3×	0.048	MECOM
Developmental Biology	1	4.8×	0.194	MECOM

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
inner cell mass cell fate commitment	2	3744.9×	1e-06	LATS1, LATS2
inner cell mass cellular morphogenesis	2	3744.9×	1e-06	LATS1, LATS2
negative regulation of cyclin-dependent protein serine/threonine kinase activity	2	1404.3×	6e-06	LATS1, LATS2
regulation of organ growth	2	1404.3×	6e-06	LATS1, LATS2
negative regulation of protein localization to nucleus	2	561.7×	3e-05	LATS1, LATS2
regulation of transforming growth factor beta receptor signaling pathway	2	535.0×	3e-05	LATS1, LATS2
hippo signaling	2	488.5×	3e-05	LATS1, LATS2
positive regulation of NLRP3 inflammasome complex assembly	2	387.4×	4e-05	LATS1, LATS2
hormone-mediated signaling pathway	2	267.5×	8e-05	LATS1, LATS2
keratinocyte differentiation	2	165.2×	2e-04	LATS1, LATS2
G1/S transition of mitotic cell cycle	2	133.8×	3e-04	LATS1, LATS2
negative regulation of canonical Wnt signaling pathway	2	78.6×	7e-04	LATS1, LATS2
intracellular protein localization	2	69.8×	8e-04	LATS1, LATS2
sister chromatid segregation	1	1872.4×	0.001	LATS1
protein phosphorylation	2	45.3×	0.002	LATS1, LATS2
negative regulation of cell growth involved in contact inhibition	1	1123.5×	0.002	LATS2
regulation of ubiquitin-dependent protein catabolic process	1	1123.5×	0.002	LATS1
positive regulation of apoptotic process	2	37.8×	0.002	LATS1, LATS2
cell division	2	30.8×	0.003	LATS1, LATS2
regulation of intracellular estrogen receptor signaling pathway	1	624.1×	0.003	LATS1
heterochromatin organization	1	432.1×	0.004	MECOM
mammary gland epithelial cell differentiation	1	401.2×	0.004	LATS1
regulation of postsynaptic density assembly	1	295.6×	0.006	LATS1
negative regulation of programmed cell death	1	244.2×	0.006	MECOM
regulation of protein-containing complex assembly	1	244.2×	0.006	LATS1
hematopoietic stem cell proliferation	1	216.1×	0.007	MECOM
regulation of actin filament polymerization	1	193.7×	0.007	LATS1
negative regulation of JNK cascade	1	187.2×	0.007	MECOM
G2/M transition of mitotic cell cycle	1	104.0×	0.013	LATS1
methylation	1	56.7×	0.022	MECOM

Therapeutics

Drugs indicated for this disease

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

Drug	Development status
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)

Drug target analysis

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

Druggability breadth: 3 of 3 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
LATS1	IBRUTINIB
LATS2	FEDRATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
LATS1	32	4
LATS2	16	4
MECOM	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
IBRUTINIB	4	LATS1
FOSTAMATINIB	4	LATS1
CAPIVASERTIB	4	LATS1
GILTERITINIB	4	LATS1
NINTEDANIB	4	LATS1, LATS2
SUNITINIB	4	LATS1, LATS2
MIDOSTAURIN	4	LATS1, LATS2
FEDRATINIB	4	LATS2
LINSITINIB	3	LATS1
CRENOLANIB	3	LATS1
LINIFANIB	3	LATS1, LATS2
ORANTINIB	3	LATS1
DEFACTINIB	3	LATS1
FASUDIL	3	LATS1
DOVITINIB	3	LATS1, LATS2
LESTAURTINIB	3	LATS1, LATS2
RUBOXISTAURIN	3	LATS1, LATS2
SU-014813	2	LATS1, LATS2
TG100-115	2	LATS1, LATS2
SCH-900776	2	LATS1
UPROSERTIB	2	LATS1
AT-9283	2	LATS1
MILCICLIB	2	LATS1
TOZASERTIB	2	LATS1, LATS2
R-406	2	LATS2
PILAVAPADIN	2	LATS2
KW-2449	1	LATS1, LATS2
PF-03758309	1	LATS1
AT-13148	1	LATS1
XL-019	1	LATS1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
LATS1	207	Binding:207
LATS2	170	Binding:170
MECOM	1	Binding:1

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
LATS1	207
LATS2	170

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

30 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.

Compound	Max phase	Cohort target (bioactivity)
IBRUTINIB	4	LATS1
FOSTAMATINIB	4	LATS1
CAPIVASERTIB	4	LATS1
GILTERITINIB	4	LATS1
NINTEDANIB	4	LATS1, LATS2
SUNITINIB	4	LATS1, LATS2
MIDOSTAURIN	4	LATS1, LATS2
FEDRATINIB	4	LATS2
LINSITINIB	3	LATS1
CRENOLANIB	3	LATS1
LINIFANIB	3	LATS1, LATS2
ORANTINIB	3	LATS1
DEFACTINIB	3	LATS1
FASUDIL	3	LATS1
DOVITINIB	3	LATS1, LATS2
LESTAURTINIB	3	LATS1, LATS2
RUBOXISTAURIN	3	LATS1, LATS2
SU-014813	2	LATS1, LATS2
TG100-115	2	LATS1, LATS2
SCH-900776	2	LATS1
UPROSERTIB	2	LATS1
AT-9283	2	LATS1
MILCICLIB	2	LATS1
TOZASERTIB	2	LATS1, LATS2
R-406	2	LATS2
PILAVAPADIN	2	LATS2
KW-2449	1	LATS1, LATS2
PF-03758309	1	LATS1
AT-13148	1	LATS1
XL-019	1	LATS1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	LATS1, LATS2
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	MECOM

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)
MECOM	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 6.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	3
PHASE1/PHASE2	2
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02535312	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Methoxyamine, Cisplatin, and Pemetrexed Disodium in Treating Patients With Advanced Solid Tumors or Mesothelioma That Cannot Be Removed by Surgery or Mesothelioma That Is Refractory to Pemetrexed Disodium and Cisplatin or Carboplatin
NCT06057935	PHASE2	RECRUITING	A Study of Additional Chemotherapy After Surgery for People With Malignant Peritoneal Mesothelioma
NCT06543069	PHASE2	RECRUITING	Sintilimab, Bevacizumab, Pemetrexed, and Cisplatin for Unresectable MPeM
NCT01592383	PHASE2	COMPLETED	Erlotinib Hydrochloride in Treating Patients With Malignant Peritoneal Mesothelioma
NCT02151448	PHASE1/PHASE2	COMPLETED	αDC1 Vaccine + Chemokine Modulatory Regimen (CKM) as Adjuvant Treatment of Peritoneal Surface Malignancies
NCT06756035	PHASE1	RECRUITING	CT-95 in Advanced Cancers Associated With Mesothelin Expression

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
ERLOTINIB HYDROCHLORIDE	4	1
INTERFERON ALFA-2B	4	1
RINTATOLIMOD	3	1
METHOXYAMINE	2	2