Digestive system cancer

Summary

Digestive system cancer (MONDO:0002516) is a cancer (an umbrella term covering 15 Mondo subtypes) with 1 cohort gene (1 GWAS associations across 4 studies; 1 CIViC-evidence somatic driver) and 42 clinical trials. Molecularly, MET Amplification confers sensitivity to Crizotinib in Gastrointestinal System Cancer (CIViC Level B); 2 further subtype–drug associations are mapped below. Top therapeutic interventions include diltiazem hydrochloride, dolasetron mesylate, and isosorbide mononitrate.

At a glance

• Classification: Cancer
• Umbrella term: 15 Mondo subtypes
• Cohort genes: 1
• GWAS associations: 1
• Clinical trials: 42
• 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 cancer
Mondo ID	MONDO:0002516
DOID	DOID:3119
ICD-10-CM	C15-C26
NCIT	C4890
UMLS	C0751075
MedGen	148231
Anatomy (UBERON)	UBERON:0001007
Is cancer (heuristic)	yes

Also known as: cancer of digestive system · digestive system cancer · gastrointestinal system cancer · GI tumor · GI tumour · malignant digestive system neoplasm · malignant gastrointestinal neoplasm · malignant gastrointestinal system neoplasm · malignant neoplasm of digestive system

Data availability: 1 GWAS association (4 studies).

Disease family

An umbrella term covering 15 Mondo subtypes.

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

Related subtypes (30): benign digestive system neoplasm, autoimmune disorder of gastrointestinal tract, gastrointestinal mucositis, diarrheal disease, pancreas disorder, hepatobiliary disorder, peptic ulcer disease, stomach disorder, intestinal disorder, Meckel diverticulum, Cronkhite-Canada syndrome, diverticulosis, small-intestinal, diverticulosis of bowel, hernia, and retinal detachment, congenital enteropathy due to enteropeptidase deficiency, hereditary mixed polyposis syndrome, caudal duplication, Moyamoya disease with early-onset achalasia, hyperplastic polyposis syndrome, thoraco-abdominal enteric duplication, digestive duplication, juvenile polyposis syndrome, umbilical cord ulceration-intestinal atresia syndrome, growth retardation-mild developmental delay-chronic hepatitis syndrome, common mesentery, neoplasm of oropharynx, gastrointestinal polyp, digestive system neuroendocrine neoplasm, digestive system infectious disorder, upper digestive tract disorder, congenital peritoneal encapsulation

Subtypes (15): gastric cancer, jaw cancer, liver cancer, gastrointestinal lymphoma, gallbladder cancer, oral cavity cancer, pharynx cancer, intestinal cancer, spleen cancer, digestive system carcinoma, esophageal cancer, malignant pancreatic neoplasm, malignant tumor of floor of mouth, digestive system melanoma, gastroesophageal cancer

Genetics & variants

GWAS landscape

1 GWAS associations across 4 studies. Top hits map to 1 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs116864126	1e-07	EDIL3-DT	?

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90399472	Zagkos L	2024	7,695	327,356	Exploring the contribution of lifestyle to the impact of education on the risk of cancer through Mendelian randomization analysis.
GCST90399474	Zagkos L	2024	5,445	328,601	Exploring the contribution of lifestyle to the impact of education on the risk of cancer through Mendelian randomization analysis.
GCST90651847	Liu TY	2025	1,606	214,673	Diversity and longitudinal records: Genetic architecture of disease associations and polygenic risk in the Taiwanese Han population.
GCST90399473	Zagkos L	2024	1,300	149,131	Exploring the contribution of lifestyle to the impact of education on the risk of cancer through Mendelian randomization analysis.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	0
Tier 2: splice/UTR	0
Tier 3: regulatory	0
Tier 4: intronic/intergenic	1

MAF distribution

Bucket	Variants
common (>=0.05)	0
low_freq (0.01-0.05)	0
rare (<0.01)	0
unknown	1

Functional consequences

Consequence	Count
intron_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs116864126	5	84558228	G>A		intron_variant	EDIL3-DT	1e-07	Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

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

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
SLTM	Act	CCRCC,LGGNOS,LUAD,NSCLC,OS,PRCC,RCC	CIViC #52

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
civic_only	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SLTM	HGNC:20709	ENSG00000137776	Q9NWH9	SAFB-like transcription modulator	civic_evidence

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SLTM	SAFB-like transcription modulator	When overexpressed, acts as a general inhibitor of transcription that eventually leads to apoptosis.

Protein-family classification

Druggable: 0 · Difficult: 0 · 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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SLTM	Other/Unknown	no		RRM_dom, SAP_dom, Nucleotide-bd_a/b_plait_sf

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
calcaneal tendon	1
sural nerve	1
tibia	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SLTM	291	ubiquitous	marker	calcaneal tendon, sural nerve, tibia

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SLTM	2,598

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SLTM	Q9NWH9	52.38

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of mRNA processing	1	887.0×	0.003	SLTM
apoptotic process	1	28.7×	0.052	SLTM
regulation of transcription by RNA polymerase II	1	11.7×	0.086	SLTM

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 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
SLTM	CABOZANTINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SLTM	1	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
CABOZANTINIB	4	SLTM

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
SLTM	14	Binding:14

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

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

Drug repurposing candidates

1 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)
CABOZANTINIB	4	SLTM

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	SLTM
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	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 42.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	26
PHASE2	6
PHASE1	6
PHASE1/PHASE2	3
PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04588246	PHASE3	TERMINATED	Comparing Whole Brain Radiotherapy Using a Technique That Avoids the Hippocampus to Stereotactic Radiosurgery in Patients With Cancer That Has Spread to the Brain and Come Back in Other Areas of the Brain After Earlier Stereotactic Radiosurgery
NCT02713269	PHASE2	ACTIVE_NOT_RECRUITING	Thermal Ablation and Spine Stereotactic Radiosurgery in Treating Patients With Spine Metastases at Risk for Compressing the Spinal Cord
NCT03337087	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Liposomal Irinotecan, Fluorouracil, Leucovorin Calcium, and Rucaparib in Treating Patients With Metastatic Pancreatic, Colorectal, Gastroesophageal, or Biliary Cancer
NCT03800693	PHASE2	RECRUITING	2 Versus 6 Hour Oxaliplatin Infusions in Patients With Gastrointestinal Cancers
NCT04111172	PHASE2	ACTIVE_NOT_RECRUITING	A Vaccine (Ad5.F35-hGCC-PADRE) for the Treatment of Gastrointestinal Adenocarcinoma
NCT06099821	PHASE2	RECRUITING	KN046 Plus Regorafenib or Apatinib in MSI-H Digestive System Cancers Resistant to PD-1/PD-L1 Blockade
NCT06855524	PHASE2	RECRUITING	Fucoidan for Preventing Chemotherapy-Related Fatigue in Patients With Gastrointestinal or Gynecological Cancer
NCT07456852	PHASE1/PHASE2	NOT_YET_RECRUITING	Vasodilator Therapy With Isosorbide Mononitrate or Diltiazem to Reduce Vasotoxicity in Patients With Gastrointestinal Cancer Receiving Fluoropyrimidine Therapy
NCT07594626	PHASE1/PHASE2	NOT_YET_RECRUITING	BMS-986504 in Combination With Pemetrexed for the Treatment of Metastatic Solid Tumors With MTAP Deletion
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
NCT02319018	PHASE1	COMPLETED	Alisertib and Combination Chemotherapy in Treating Patients With Gastrointestinal Tumors
NCT02333188	PHASE1	COMPLETED	Genetic Analysis-Guided Dosing of FOLFIRABRAX in Treating Patients With Advanced Gastrointestinal Cancer
NCT02530398	PHASE1	UNKNOWN	A Tolerance Trial of Cinobufacini Injection Intraperitoneal Perfusion on Digestive System Cancer With Ascites
NCT04130763	PHASE1	COMPLETED	Fecal Microbiota Transplant (FMT) Capsule for Improving the Efficacy of Anti- PD-1
NCT05107219	PHASE1	COMPLETED	GCC Agonist Signal in the Small Intestine
NCT05639153	PHASE1	TERMINATED	A Trial to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of DR30303 in Patients With Advanced Solid Tumors
NCT00991094	Not specified	RECRUITING	Data Collection for the Assessment of Acute and Late Normal Tissue in Patients Treated With Proton Therapy
NCT02221700	Not specified	ACTIVE_NOT_RECRUITING	Massage Therapy in Reducing Chemotherapy-Induced Peripheral Neuropathy in Patients With Gastrointestinal or Breast Malignancies
NCT04221893	Not specified	RECRUITING	Radiation Therapy for the Treatment of Metastatic Gastrointestinal Cancers
NCT04629677	Not specified	RECRUITING	Evaluation of Portal Vein Stenting in Patients With Portal Vein Stenosis and Gastrointestinal Cancers
NCT04986566	Not specified	ACTIVE_NOT_RECRUITING	Perioperative Telemonitoring to Optimize Cancer Care and Outcomes
NCT05038254	Not specified	ACTIVE_NOT_RECRUITING	Enhanced Outpatient Symptom Management to Reduce Acute Care Visits Due to Chemotherapy-Related Adverse Events
NCT05179486	Not specified	RECRUITING	Molecular Epidemiology of Biliary Tree Cancers
NCT06223230	Not specified	RECRUITING	Nutritional Psychological Intervention and Vomit-free Management on Survival and Quality of Life in Advanced Gastrointestinal Tumors
NCT06715839	Not specified	RECRUITING	Target-specific immunoPET Imaging of Digestive System Carcinoma
NCT06940102	Not specified	RECRUITING	Real-World Study on Nano-Crystalline Megestrol Acetate for Cachexia in TKI-Treated Advanced Digestive Tumors
NCT07215624	Not specified	RECRUITING	Surgical Thromboprophylaxis Practices in Oncology Patients Within the NCORP Network, STOP-VTE Study
NCT07283939	Not specified	RECRUITING	Studying the PAGODA Algorithm for Chemotherapy Dose Changes to Prevent Unplanned Treatment Delays
NCT07383935	Not specified	RECRUITING	Stress Ball Use During Chemotherapy in Gastrointestinal Cancer Patients
NCT07606287	Not specified	NOT_YET_RECRUITING	Studying the Workflow of the American College of Surgeons Geriatric Surgery Program to Improve Clinical Outcomes in Older Adults Undergoing Surgery at the James Cancer Hospital
NCT02192333	Not specified	COMPLETED	Survivorship Care in Reducing Symptoms in Young Adult Cancer Survivors
NCT02312167	Not specified	COMPLETED	Feasibility Study for Robotic Endomicroscopy to Better Define Resection Strategies (PERSEE)
NCT02356471	Not specified	COMPLETED	Consumer-Based Activity Monitor in Evaluating and Measuring Activity of Older Patients With Abdominal Cancer Undergoing Surgery
NCT02550119	Not specified	TERMINATED	Dolasetron Mesylate and Dexamethasone With or Without Aprepitant in Preventing Nausea and Vomiting in Patients Undergoing Oxaliplatin-Containing Chemotherapy for Gastrointestinal Malignancy
NCT03172403	Not specified	TERMINATED	Skeletal Muscle Expression of Myostatin and Cancer of Digestive System Associated Cachexia
NCT03267524	Not specified	COMPLETED	Walking for Recovery From Surgery in Improving Quality of Life in Older Adults With Lung or Gastrointestinal Cancer and Their Family Caregivers
NCT03563352	Not specified	WITHDRAWN	Nutritional Preferences and Product Accessibility in Oral Nutritional Supplements in Participants With Breast, Colorectal, Upper Gastrointestinal, or Prostate Cancer
NCT03763526	Not specified	COMPLETED	Association Between Perioperative Nutritional Status and Surgical Outcome in Digestive System Cancer Patients
NCT04501913	Not specified	COMPLETED	Remote Telemonitoring of Patient-Generated Physiologic Health Data and Patient-Reported Outcomes
NCT05018208	Not specified	COMPLETED	Remote Monitoring in Cancer Care: A Platform Study

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
DILTIAZEM HYDROCHLORIDE	4	1
DOLASETRON MESYLATE	4	1
ISOSORBIDE MONONITRATE	4	1
LINACLOTIDE	4	1
MEMANTINE	4	1
PLECANATIDE	4	1
RUCAPARIB	4	1
ALISERTIB	3	1
ERFONRILIMAB	3	1
IRINOTECAN SUCROSOFATE	3	1
CHEMBL2373322	0	1

Precision-medicine subtype map (CIViC)

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

Molecular subtype	Therapy	Effect	Level	CIViC
MET Amplification	Crizotinib	Sensitivity/Response	CIViC B	EID11454
KIT V559	Imatinib + Dasatinib	Sensitivity/Response	CIViC D	EID3030
KIT Overexpression	Imatinib	Resistance	CIViC D	EID10152