Digestive system carcinoma

Summary

Digestive system carcinoma (MONDO:0006181) is a cancer (an umbrella term covering 16 Mondo subtypes) with 2 cohort genes (2 CIViC-evidence somatic drivers; 2 ClinVar predisposition records) and 17 clinical trials. Molecularly, TMB mTMB confers sensitivity to Immune Checkpoint Inhibitor in Gastrointestinal Carcinoma (CIViC Level B); 2 further subtype–drug associations are mapped below. Top therapeutic interventions include lorcaserin, fludarabine phosphate, and indusatumab vedotin.

At a glance

• Classification: Cancer
• Umbrella term: 16 Mondo subtypes
• Cohort genes: 2
• ClinVar variants: 2
• Clinical trials: 17
• Precision-medicine evidence (CIViC): 3 subtype–drug associations

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	digestive system carcinoma
Mondo ID	MONDO:0006181
EFO	EFO:1000218
DOID	DOID:0050922
NCIT	C96963
UMLS	C0151544
MedGen	57467
Anatomy (UBERON)	UBERON:0001007
Is cancer (heuristic)	yes

Also known as: carcinoma of digestive system · carcinoma of the gastrointestinal system · digestive system carcinoma · gastrointestinal carcinoma · gastrointestinal carcinoma (disease) · gastrointestinal system carcinoma

Data availability: 2 ClinVar variants · 1 HPO phenotype.

Disease family

An umbrella term covering 16 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › digestive system disorder › digestive system cancer › digestive system carcinoma

Related subtypes (14): gastric cancer, jaw cancer, liver cancer, gastrointestinal lymphoma, gallbladder cancer, oral cavity cancer, pharynx cancer, intestinal cancer, spleen cancer, esophageal cancer, malignant pancreatic neoplasm, malignant tumor of floor of mouth, digestive system melanoma, gastroesophageal cancer

Subtypes (16): maxillary sinus carcinoma, gastroesophageal junction adenocarcinoma, gallbladder carcinoma, intestine carcinoma in situ, gastric carcinoma, exocrine pancreatic carcinoma, small intestine carcinoma, pancreatic endocrine carcinoma, ameloblastic carcinoma, digestive system mixed adenoneuroendocrine carcinoma, carcinoma of liver and intrahepatic biliary tract, carcinoma of esophagus, carcinoma of floor of mouth, carcinoma of pharynx, colorectal carcinoma, oral cavity 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

ClinVar germline variants

2 retrieved; paginated sample, class counts are floors:

1 uncertain significance, 1 conflicting classifications of pathogenicity; risk factor

ClinVar	Variant (HGVS)	Gene	Classification	Review
5591	NM_007194.4(CHEK2):c.470T>C (p.Ile157Thr)	CHEK2	Conflicting classifications of pathogenicity; risk factor	criteria provided, conflicting classifications
523433	NM_000501.4(ELN):c.898A>T (p.Thr300Ser)	ELN	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 9 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
CHEK2	Act	BRCA	CIViC #8950
ELN	LoF	BRCA,CSCC

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CHEK2	Orphanet:1331	Familial prostate cancer
CHEK2	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
CHEK2	Orphanet:440437	Familial colorectal cancer Type X
CHEK2	Orphanet:524	Li-Fraumeni syndrome
CHEK2	Orphanet:668	Osteosarcoma
ELN	Orphanet:3193	Supravalvular aortic stenosis
ELN	Orphanet:90348	Autosomal dominant cutis laxa
ELN	Orphanet:904	Williams syndrome
ELN	Orphanet:91387	Familial thoracic aortic aneurysm and aortic dissection

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
CHEK2	HGNC:16627	ENSG00000183765	O96017	Serine/threonine-protein kinase Chk2	clinvar
ELN	HGNC:3327	ENSG00000049540	P15502	Elastin	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CHEK2	Serine/threonine-protein kinase Chk2	Serine/threonine-protein kinase which is required for checkpoint-mediated cell cycle arrest, activation of DNA repair and apoptosis in response to the presence of DNA double-strand breaks.
ELN	Elastin	Major structural protein of tissues such as aorta and nuchal ligament, which must expand rapidly and recover completely.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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	1	13.9×	0.142
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CHEK2	Kinase	yes	2.7.11.1	FHA_dom, Prot_kinase_dom, Ser/Thr_kinase_AS
ELN	Other/Unknown	no		Tropoelastin

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
lower esophagus mucosa	1
male germ line stem cell (sensu Vertebrata) in testis	1
primordial germ cell in gonad	1
ascending aorta	1
descending thoracic aorta	1
thoracic aorta	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CHEK2	183	ubiquitous	marker	primordial germ cell in gonad, lower esophagus mucosa, male germ line stem cell (sensu Vertebrata) in testis
ELN	227	broad	marker	descending thoracic aorta, ascending aorta, thoracic aorta

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CHEK2	4,795
ELN	2,692

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CHEK2	O96017	38

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ELN	P15502	36.20

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 11. 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
Stabilization of p53	1	380.7×	0.013	CHEK2
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	1	335.9×	0.013	CHEK2
Regulation of TP53 Activity through Methylation	1	271.9×	0.013	CHEK2
Elastic fibre formation	1	167.9×	0.013	ELN
Molecules associated with elastic fibres	1	154.3×	0.013	ELN
Regulation of TP53 Degradation	1	146.4×	0.013	CHEK2
Ubiquitin-Mediated Degradation of Phosphorylated Cdc25A	1	102.0×	0.015	CHEK2
Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks	1	73.2×	0.017	CHEK2
G2/M DNA damage checkpoint	1	60.1×	0.017	CHEK2
Degradation of the extracellular matrix	1	58.9×	0.017	ELN
Regulation of TP53 Activity through Phosphorylation	1	58.9×	0.017	CHEK2

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 DNA damage checkpoint	1	2808.7×	0.007	CHEK2
mitotic DNA damage checkpoint signaling	1	2106.5×	0.007	CHEK2
cellular response to bisphenol A	1	1685.2×	0.007	CHEK2
response to glycoside	1	1203.7×	0.007	CHEK2
positive regulation of anoikis	1	936.2×	0.007	CHEK2
thymocyte apoptotic process	1	702.2×	0.007	CHEK2
regulation of smooth muscle cell proliferation	1	648.1×	0.007	ELN
regulation of autophagosome assembly	1	561.7×	0.007	CHEK2
replicative senescence	1	495.6×	0.007	CHEK2
mitotic intra-S DNA damage checkpoint signaling	1	468.1×	0.007	CHEK2
extracellular matrix assembly	1	468.1×	0.007	ELN
cellular response to stress	1	421.3×	0.007	CHEK2
regulation of protein catabolic process	1	421.3×	0.007	CHEK2
signal transduction in response to DNA damage	1	401.2×	0.007	CHEK2
stress fiber assembly	1	383.0×	0.007	ELN
respiratory gaseous exchange by respiratory system	1	312.1×	0.008	ELN
cellular response to gamma radiation	1	300.9×	0.008	CHEK2
regulation of actin filament polymerization	1	290.6×	0.008	ELN
blood circulation	1	255.3×	0.008	ELN
intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator	1	247.8×	0.008	CHEK2
aortic valve morphogenesis	1	216.1×	0.009	ELN
DNA damage checkpoint signaling	1	195.9×	0.009	CHEK2
regulation of signal transduction by p53 class mediator	1	191.5×	0.009	CHEK2
DNA damage response, signal transduction by p53 class mediator	1	179.3×	0.009	CHEK2
mitotic spindle assembly	1	172.0×	0.009	CHEK2
intrinsic apoptotic signaling pathway in response to DNA damage	1	162.0×	0.009	CHEK2
G2/M transition of mitotic cell cycle	1	156.0×	0.009	CHEK2
outflow tract morphogenesis	1	153.2×	0.009	ELN
skeletal muscle tissue development	1	145.3×	0.009	ELN
cellular response to xenobiotic stimulus	1	120.4×	0.011	CHEK2

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 2 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
CHEK2	NERATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CHEK2	30	4
ELN	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
NERATINIB	4	CHEK2
BOSUTINIB	4	CHEK2
BRIGATINIB	4	CHEK2
SUNITINIB	4	CHEK2
GEFITINIB	4	CHEK2
FASUDIL	3	CHEK2
CEDIRANIB	3	CHEK2
DOVITINIB	3	CHEK2
LESTAURTINIB	3	CHEK2
RUBOXISTAURIN	3	CHEK2
DORAMAPIMOD	2	CHEK2
FORETINIB	2	CHEK2
SU-014813	2	CHEK2
CENISERTIB	2	CHEK2
ILORASERTIB	2	CHEK2
CEP-11981	2	CHEK2
DEFOSBARASERTIB	2	CHEK2
PREXASERTIB	2	CHEK2
BI-2536	2	CHEK2
UCN-01	2	CHEK2
PF-00562271	1	CHEK2
KW-2449	1	CHEK2
RG-1530	1	CHEK2
MLN-8054	1	CHEK2
PF-03758309	1	CHEK2
SRA-737	1	CHEK2
SNS-314	1	CHEK2
CYC-116	1	CHEK2
GSK-690693	1	CHEK2
AST-487	1	CHEK2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
CHEK2	690	Binding:687, Functional:2, ADMET:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
CHEK2	2.7.11.1	non-specific serine/threonine protein kinase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
CHEK2	690

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).

Drug repurposing candidates

30 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)
NERATINIB	4	CHEK2
BOSUTINIB	4	CHEK2
BRIGATINIB	4	CHEK2
SUNITINIB	4	CHEK2
GEFITINIB	4	CHEK2
FASUDIL	3	CHEK2
CEDIRANIB	3	CHEK2
DOVITINIB	3	CHEK2
LESTAURTINIB	3	CHEK2
RUBOXISTAURIN	3	CHEK2
DORAMAPIMOD	2	CHEK2
FORETINIB	2	CHEK2
SU-014813	2	CHEK2
CENISERTIB	2	CHEK2
ILORASERTIB	2	CHEK2
CEP-11981	2	CHEK2
DEFOSBARASERTIB	2	CHEK2
PREXASERTIB	2	CHEK2
BI-2536	2	CHEK2
UCN-01	2	CHEK2
PF-00562271	1	CHEK2
KW-2449	1	CHEK2
RG-1530	1	CHEK2
MLN-8054	1	CHEK2
PF-03758309	1	CHEK2
SRA-737	1	CHEK2
SNS-314	1	CHEK2
CYC-116	1	CHEK2
GSK-690693	1	CHEK2
AST-487	1	CHEK2

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	CHEK2
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	ELN

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)
ELN	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 17.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE1	7
Not specified	7
PHASE2	2
PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06500455	PHASE3	RECRUITING	Testing Longer Duration Radiation Therapy Versus the Usual Radiation Therapy in Patients With Cancer That Has Spread to the Brain
NCT04505553	PHASE2	COMPLETED	Oral Cryotherapy Plus Acupressure and Acupuncture Versus Oral Cryotherapy for Decreasing Chemotherapy-Induced Peripheral Neuropathy From Oxaliplatin-Based Chemotherapy in Patients With Gastrointestinal Cancer
NCT06690281	PHASE2	WITHDRAWN	A Phase II Study of Adjuvant Immunotherapy Targeting KRAS G12D, KRAS G12V, or TP53 R175H for Participants With Advanced Gastrointestinal Malignancies
NCT06414733	PHASE1	RECRUITING	HER-2 B Cell Peptide Vaccine
NCT06430372	PHASE1	RECRUITING	Study of VEGF-A Targeting NIR-II Fluorescence Endoscopy in the Gastrointestinal Tract
NCT01552434	PHASE1	TERMINATED	Bevacizumab and Temsirolimus Alone or in Combination With Valproic Acid or Cetuximab in Treating Patients With Advanced or Metastatic Malignancy or Other Benign Disease
NCT02391038	PHASE1	TERMINATED	MLN0264 in Previously Treated Asian Participants With Advanced Gastrointestinal Carcinoma or Metastatic or Recurrent Gastric or Gastroesophageal Junction Adenocarcinoma Expressing Guanylyl Cyclase C
NCT02757391	PHASE1	TERMINATED	CD8+ T Cell Therapy and Pembrolizumab in Treating Patients With Metastatic Gastrointestinal Tumors
NCT04205071	PHASE1	WITHDRAWN	Lorcaserin in Treating Chemotherapy-Induced Peripheral Neuropathy in Patients With Stage I-IV Gastrointestinal or Breast Cancer
NCT04535401	PHASE1	UNKNOWN	Testing the Addition of an Anticancer Drug, BAY 1895344, to the Usual Chemotherapy With FOLFIRI in Advanced or Metastatic Cancers of the Stomach and Intestines
NCT04475640	Not specified	RECRUITING	Cancer Genetic Testing in Ethnic Populations
NCT04596384	Not specified	ACTIVE_NOT_RECRUITING	Home Base Telemonitoring in Gastrointestinal, Genitourinary, or Gynecologic Cancer Patients Undergoing Abdominal Surgery
NCT06715839	Not specified	RECRUITING	Target-specific immunoPET Imaging of Digestive System Carcinoma
NCT01262040	Not specified	COMPLETED	Narrow Band Imaging (NBI): A Novel Imaging Modality in Minimally Invasive
NCT02649569	Not specified	COMPLETED	Continuous Activity Monitoring During Fractionated Radiotherapy in Patients With Head and Neck, Lung, or Gastrointestinal Cancer
NCT02871999	Not specified	COMPLETED	Clinical Trial on Acupuncture Adjuvant Treatment in the Pain After the Surgery of Gastrointestinal Carcinoma
NCT03528863	Not specified	COMPLETED	Web-based Mindfulness Meditation in Reducing Distress in Participants With Metastatic Gastrointestinal Cancer and Their Caregivers

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
LORCASERIN	4	3
FLUDARABINE PHOSPHATE	4	1
INDUSATUMAB VEDOTIN	2	1
ELIMUSERTIB	1	1

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 3 predictive associations from 3 curated evidence items.

Molecular subtype	Therapy	Effect	Level	CIViC
TMB mTMB	Immune Checkpoint Inhibitor	Sensitivity/Response	CIViC B	EID12823
ALK Fusion	Alectinib + Crizotinib + Entrectinib	Sensitivity/Response	CIViC C	EID10324
KRAS Overexpression	Alisertib	Sensitivity/Response	CIViC D	EID10154