Gastric adenocarcinoma

Summary

Gastric adenocarcinoma (MONDO:0005036) is a disease (an umbrella term covering 9 Mondo subtypes) with 24 cohort genes (7 GWAS associations across 1 studies) and 365 clinical trials. The dominant Reactome pathway is Constitutive Signaling by Aberrant PI3K in Cancer (5 cohort genes). Molecularly, ERBB2 Amplification confers sensitivity to Trastuzumab in Gastric Adenocarcinoma (CIViC Level A); 19 further subtype–drug associations are mapped below. Top therapeutic interventions include ramucirumab, irinotecan, and tipiracil.

At a glance

• Umbrella term: 9 Mondo subtypes
• Cohort genes: 24
• GWAS associations: 7
• ClinVar variants: 1
• Clinical trials: 365
• Precision-medicine evidence (CIViC): 20 subtype–drug associations

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	gastric adenocarcinoma
Mondo ID	MONDO:0005036
EFO	EFO:0000503
Orphanet	464463
DOID	DOID:3717
ICD-11	1855471719
NCIT	C4004
SNOMED CT	408647009
UMLS	C0278701
MedGen	82961
GARD	0027713
Anatomy (UBERON)	UBERON:0000945
Is cancer (heuristic)	no

Also known as: adenocarcinoma - stomach · adenocarcinoma of stomach · adenocarcinoma of the stomach · gastric (stomach) adenocarcinoma · gastric adenocarcinoma · STAD · stomach adenocarcinoma

Data availability: 1 ClinVar variant · 7 GWAS associations (1 study) · 198 cell lines · 74 intOGen driver records.

Disease family

An umbrella term covering 9 Mondo subtypes.

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

Related subtypes (11): gastric cardia carcinoma, gastric fundus carcinoma, gastric pylorus carcinoma, gastric body carcinoma, stomach carcinoma in situ, gastric small cell neuroendocrine carcinoma, gastric squamous cell carcinoma, Epstein-Barr virus-associated gastric carcinoma, hereditary gastric cancer, carcinoma of stomach, salivary gland type, undifferentiated carcinoma of stomach

Subtypes (9): microinvasive gastric cancer, gastric cardia adenocarcinoma, diffuse gastric adenocarcinoma, gastric intestinal type adenocarcinoma, gastric tubular adenocarcinoma, gastric papillary adenocarcinoma, mucinous gastric adenocarcinoma, signet ring cell gastric adenocarcinoma, CTNNA1-related diffuse gastric and lobular breast cancer syndrome

Genetics & variants

GWAS landscape

7 GWAS associations across 1 studies. Top hits map to 5 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs140081212	2e-08	GBA1LP, GBA1LP	G	1.27
chr2:85874332	8e-08		T	12.7
chr11:107643195	2e-07		T	4.84
chr11:102118158-A	4e-07		A	4.88
chr11:107629783	1e-06		A	7.78
rs2294008	1e-06	JRK, PSCA	T	1.21
rs55864139	7e-06	CHD6	A	3.12

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST002990	Helgason H	2015	2,043	202,533	Loss-of-function variants in ATM confer risk of gastric cancer.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	1
Tier 2: splice/UTR	1
Tier 3: regulatory	0
Tier 4: intronic/intergenic	5

MAF distribution

Bucket	Variants
common (>=0.05)	2
low_freq (0.01-0.05)	0
rare (<0.01)	3
unknown	2

Functional consequences

Consequence	Count
unknown	4
intron_variant	1
5_prime_UTR_variant	1
missense_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs140081212	1	155215184		0.354	intron_variant	GBA1LP, GBA1LP	2e-08	Tier 4: intronic/intergenic
chr2:85874332							8e-08	Tier 4: intronic/intergenic
chr11:107643195				0.002			2e-07	Tier 4: intronic/intergenic
chr11:102118158-A				0.01			4e-07	Tier 4: intronic/intergenic
chr11:107629783							1e-06	Tier 4: intronic/intergenic
rs2294008	8	142680513	C>T	0.471	5_prime_UTR_variant	JRK, PSCA	1e-06	Tier 2: splice/UTR
rs55864139	20	41420939	T>A,C,G	0.003	missense_variant	CHD6	7e-06	Tier 1: coding

ClinVar germline variants

1 retrieved; paginated sample, class counts are floors:

1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
12245	NM_004360.5(CDH1):c.1018A>G (p.Thr340Ala)	CDH1	Benign	reviewed by expert panel

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 104 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ATM	Orphanet:100	Ataxia-telangiectasia
ATM	Orphanet:1331	Familial prostate cancer
ATM	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
ATM	Orphanet:227535	Hereditary breast cancer
ATM	Orphanet:370109	Ataxia-telangiectasia variant
ATM	Orphanet:440437	Familial colorectal cancer Type X
ATM	Orphanet:52416	Mantle cell lymphoma
ATM	Orphanet:67038	B-cell chronic lymphocytic leukemia
TP53	Orphanet:1333	Familial pancreatic carcinoma
TP53	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
TP53	Orphanet:1501	Adrenocortical carcinoma
TP53	Orphanet:210159	Adult hepatocellular carcinoma
TP53	Orphanet:251576	Gliosarcoma
TP53	Orphanet:251579	Giant cell glioblastoma
TP53	Orphanet:251899	Choroid plexus carcinoma
TP53	Orphanet:2807	Papilloma of choroid plexus
TP53	Orphanet:293199	Pleomorphic rhabdomyosarcoma
TP53	Orphanet:3318	Essential thrombocythemia
TP53	Orphanet:524	Li-Fraumeni syndrome
TP53	Orphanet:52688	Myelodysplastic syndrome
TP53	Orphanet:585909	B-lymphoblastic leukemia/lymphoma with t(9;22)(q34.1;q11.2)
TP53	Orphanet:667662	Breast implant-associated anaplastic large cell lymphoma
TP53	Orphanet:668	Osteosarcoma
TP53	Orphanet:67038	B-cell chronic lymphocytic leukemia
TP53	Orphanet:70573	Small cell lung cancer
TP53	Orphanet:96253	Cushing disease
TP53	Orphanet:99756	Alveolar rhabdomyosarcoma
TP53	Orphanet:99757	Embryonal rhabdomyosarcoma
TYMS	Orphanet:1775	Dyskeratosis congenita
CXCR4	Orphanet:51636	WHIM syndrome
DNMT1	Orphanet:314404	Autosomal dominant cerebellar ataxia-deafness-narcolepsy syndrome
DNMT1	Orphanet:456318	Hereditary sensory neuropathy-deafness-dementia syndrome
EGFR	Orphanet:251576	Gliosarcoma
EGFR	Orphanet:251579	Giant cell glioblastoma
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
FGFR1	Orphanet:168953	Myeloid/lymphoid neoplasm associated with FGFR1 rearrangement
FGFR1	Orphanet:2117	Hartsfield syndrome
FGFR1	Orphanet:220386	Semilobar holoprosencephaly
FGFR1	Orphanet:2396	Encephalocraniocutaneous lipomatosis
FGFR1	Orphanet:251576	Gliosarcoma
FGFR1	Orphanet:251579	Giant cell glioblastoma
FGFR1	Orphanet:251615	Pilomyxoid astrocytoma
FGFR1	Orphanet:2645	Osteoglosphonic dysplasia
FGFR1	Orphanet:280200	Microform holoprosencephaly
FGFR1	Orphanet:314950	Primary hypereosinophilic syndrome
FGFR1	Orphanet:3157	Septo-optic dysplasia spectrum
FGFR1	Orphanet:3366	Non-syndromic metopic craniosynostosis

Cohort genes → proteins

24 cohort genes, 24 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	5
civic_only	17
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ATM	HGNC:795	ENSG00000149311	Q13315	Serine-protein kinase ATM	gwas,civic_evidence
RPS6	HGNC:10429	ENSG00000137154	P62753	Small ribosomal subunit protein eS6	civic_evidence
TP53	HGNC:11998	ENSG00000141510	P04637	Cellular tumor antigen p53	civic_evidence
TYMS	HGNC:12441	ENSG00000176890	P04818	Thymidylate synthase	civic_evidence
HSPH1	HGNC:16969	ENSG00000120694	Q92598	Heat shock protein 105 kDa	civic_evidence
PBK	HGNC:18282	ENSG00000168078	Q96KB5	Lymphokine-activated killer T-cell-originated protein kinase	civic_evidence
SLTM	HGNC:20709	ENSG00000137776	Q9NWH9	SAFB-like transcription modulator	civic_evidence
CXCR4	HGNC:2561	ENSG00000121966	P61073	C-X-C chemokine receptor type 4	civic_evidence
RICTOR	HGNC:28611	ENSG00000164327	Q6R327	Rapamycin-insensitive companion of mTOR	civic_evidence
DNMT1	HGNC:2976	ENSG00000130816	P26358	DNA (cytosine-5)-methyltransferase 1	civic_evidence
EGFR	HGNC:3236	ENSG00000146648	P00533	Epidermal growth factor receptor	civic_evidence
EIF4EBP1	HGNC:3288	ENSG00000187840	Q13541	Eukaryotic translation initiation factor 4E-binding protein 1	civic_evidence
ERBB2	HGNC:3430	ENSG00000141736	P04626	Receptor tyrosine-protein kinase erbB-2	civic_evidence
FGFR1	HGNC:3688	ENSG00000077782	P11362	Fibroblast growth factor receptor 1	civic_evidence
FGFR2	HGNC:3689	ENSG00000066468	P21802	Fibroblast growth factor receptor 2	civic_evidence
PIK3CA	HGNC:8975	ENSG00000121879	P42336	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	civic_evidence
PSMB8	HGNC:9545	ENSG00000204264	P28062	Proteasome subunit beta type-8	civic_evidence
PTEN	HGNC:9588	ENSG00000171862	P60484	Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN	civic_evidence
CDH1	HGNC:1748	ENSG00000039068	P12830	Cadherin-1	clinvar
CHD6	HGNC:19057	ENSG00000124177	Q8TD26	ATP-dependent chromatin remodeler CHD6	gwas
HCN3	HGNC:19183	ENSG00000143630	Q9P1Z3	Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3	gwas
MTX1	HGNC:7504	ENSG00000173171	Q13505	Metaxin-1	gwas
MUC1	HGNC:7508	ENSG00000185499	P15941	Mucin-1	gwas
PSCA	HGNC:9500	ENSG00000167653	O43653	Prostate stem cell antigen	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ATM	Serine-protein kinase ATM	Serine/threonine protein kinase which activates checkpoint signaling upon double strand breaks (DSBs), apoptosis and genotoxic stresses such as ionizing ultraviolet A light (UVA), thereby acting as a DNA damage sensor.
RPS6	Small ribosomal subunit protein eS6	Component of the 40S small ribosomal subunit.
TP53	Cellular tumor antigen p53	Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence.
TYMS	Thymidylate synthase	Catalyzes the reductive methylation of 2’-deoxyuridine 5’-monophosphate (dUMP) to thymidine 5’-monophosphate (dTMP), using the cosubstrate, 5,10- methylenetetrahydrofolate (CH2H4folate) as a 1-carbon donor and reductant and contributes to…
HSPH1	Heat shock protein 105 kDa	Acts as a nucleotide-exchange factor (NEF) for chaperone proteins HSPA1A and HSPA1B, promoting the release of ADP from HSPA1A/B thereby triggering client/substrate protein release.
PBK	Lymphokine-activated killer T-cell-originated protein kinase	Phosphorylates MAP kinase p38.
SLTM	SAFB-like transcription modulator	When overexpressed, acts as a general inhibitor of transcription that eventually leads to apoptosis.
CXCR4	C-X-C chemokine receptor type 4	Receptor for the C-X-C chemokine CXCL12/SDF-1 that transduces a signal by increasing intracellular calcium ion levels and enhancing MAPK1/MAPK3 activation.
RICTOR	Rapamycin-insensitive companion of mTOR	Component of the mechanistic target of rapamycin complex 2 (mTORC2), which transduces signals from growth factors to pathways involved in proliferation, cytoskeletal organization, lipogenesis and anabolic output.
DNMT1	DNA (cytosine-5)-methyltransferase 1	DNA methyltransferase that methylates CpG residues.
EGFR	Epidermal growth factor receptor	Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses.
EIF4EBP1	Eukaryotic translation initiation factor 4E-binding protein 1	Repressor of translation initiation that regulates EIF4E activity by preventing its assembly into the eIF4F complex: hypophosphorylated form competes with EIF4G1/EIF4G3 and strongly binds to EIF4E, leading to repress translation.
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.
FGFR1	Fibroblast growth factor receptor 1	Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of embryonic development, cell proliferation, differentiation and migration.
FGFR2	Fibroblast growth factor receptor 2	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, migration and apoptosis, and in the regulation of embryonic de…
PIK3CA	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	Phosphoinositide-3-kinase (PI3K) phosphorylates phosphatidylinositol (PI) and its phosphorylated derivatives at position 3 of the inositol ring to produce 3-phosphoinositides.
PSMB8	Proteasome subunit beta type-8	The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH.
PTEN	Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN	Dual-specificity protein phosphatase, dephosphorylating tyrosine-, serine- and threonine-phosphorylated proteins.
CDH1	Cadherin-1	Cadherins are calcium-dependent cell adhesion proteins.
CHD6	ATP-dependent chromatin remodeler CHD6	ATP-dependent chromatin-remodeling factor.
HCN3	Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3	Hyperpolarization-activated ion channel that are permeable to sodium and potassium ions, with an about 3:1 preference for potassium ions.
MTX1	Metaxin-1	Involved in transport of proteins into the mitochondrion.
MUC1	Mucin-1	The alpha subunit has cell adhesive properties.
PSCA	Prostate stem cell antigen	May be involved in the regulation of cell proliferation.

Protein-family classification

Druggable: 11 · Difficult: 2 · Unknown: 11 · Druggable fraction: 0.46

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	7	8.1×	1e-04
Ion channel	1	4.7×	0.584
Phosphatase	1	3.5×	0.584
GPCR	1	1.0×	0.883
Other/Unknown	11	0.8×	0.883
Transcription factor	2	0.7×	0.883
Enzyme (other)	1	0.5×	0.883

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ATM	Kinase	yes	2.7.11.1	PI3/4_kinase_cat_dom, PIK-rel_kinase_FAT, FATC_dom
RPS6	Other/Unknown	no		Ribosomal_eS6, Ribosomal_eS6-like, Ribosomal_eS6_CS
TP53	Transcription factor	no		p53_tumour_suppressor, p53-like_TF_DNA-bd_sf, p53_tetrameristn
TYMS	Enzyme (other)	yes	2.1.1.45	Thymidylate_synthase, Thymidylate_synthase_AS, Thymidate_synth/dCMP_Mease_dom
HSPH1	Other/Unknown	no		Hsp_70_fam, Heat_shock_70_CS, HSP70_peptide-bd_sf
PBK	Kinase	yes		Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
SLTM	Other/Unknown	no		RRM_dom, SAP_dom, Nucleotide-bd_a/b_plait_sf
CXCR4	GPCR	yes		GPCR_Rhodpsn, Chemokine_rcpt, CXCR4/ACKR2
RICTOR	Other/Unknown	no		ARM-type_fold, Pianissimo_N, Pianissimo_fam
DNMT1	Transcription factor	no	2.1.1.37	BAH_dom, C5_MeTfrase, Znf_CXXC
EGFR	Kinase	yes	2.7.10.1	Rcpt_L-dom, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom
EIF4EBP1	Other/Unknown	no		EIF4EBP
ERBB2	Kinase	yes	2.7.10.1	Rcpt_L-dom, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom
FGFR1	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Ig_sub2
FGFR2	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Ig_sub2
PIK3CA	Kinase	yes	2.7.1.137	PI3K_Ras-bd_dom, PI3/4_kinase_cat_dom, PI3K_accessory_dom
PSMB8	Other/Unknown	no		Pept_T1A_subB, Proteasome_sua/b, Proteasome_bsu_CS
PTEN	Phosphatase	yes	3.1.3.16	Tyr_Pase_dom, Tyr_Pase_cat, Tensin_C2-dom
CDH1	Other/Unknown	no		Cadherin_Y-type_LIR, Cadherin-like_dom, Cadherin_pro_dom
CHD6	Other/Unknown	no		SNF2_N, Chromo/chromo_shadow_dom, Helicase_C-like
HCN3	Ion channel	yes		cNMP-bd_dom, K_chnl_volt-dep_EAG/ELK/ERG, Ion_trans_dom
MTX1	Other/Unknown	no		Sam37/metaxin_N, Metaxin_GST, Glutathione-S-Trfase_C_sf
MUC1	Other/Unknown	no		SEA_dom, SEA_dom_sf
PSCA	Other/Unknown	no		LY6_UPA_recep-like, Toxin/TOLIP, Snake_toxin-like_sf

Expression context

Cohort genes with no expression data: 0.

24 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)	24
unknown	0

Top tissues across cohort

Tissue	Cohort genes
calcaneal tendon	6
sural nerve	4
corpus callosum	3
ventricular zone	3
lower esophagus mucosa	3
sperm	2
gingival epithelium	2
endothelial cell	2
colonic epithelium	1
mammary duct	1
skin of hip	1
upper leg skin	1
ganglionic eminence	1
tendon of biceps brachii	1
embryo	1
trabecular bone tissue	1
bronchial epithelial cell	1
epithelium of bronchus	1
primordial germ cell in gonad	1
male germ cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ATM	286	ubiquitous	marker	calcaneal tendon, colonic epithelium, corpus callosum
RPS6	311	ubiquitous	marker	skin of hip, upper leg skin, mammary duct
TP53	223	ubiquitous	marker	ventricular zone, ganglionic eminence, tendon of biceps brachii
TYMS	262	ubiquitous	marker	ventricular zone, embryo, trabecular bone tissue
HSPH1	290	ubiquitous	marker	primordial germ cell in gonad, bronchial epithelial cell, epithelium of bronchus
PBK	189	ubiquitous	marker	ventricular zone, sperm, male germ cell
SLTM	291	ubiquitous	marker	calcaneal tendon, sural nerve, tibia
CXCR4	281	ubiquitous	marker	bone marrow, thymus, lymph node
RICTOR	263	ubiquitous	marker	kidney epithelium, corpus callosum, tibialis anterior
DNMT1	266	ubiquitous	marker	oocyte, secondary oocyte, sural nerve
EGFR	285	ubiquitous	marker	nipple, gingiva, gingival epithelium
EIF4EBP1	251	ubiquitous	marker	body of pancreas, parotid gland, lower esophagus mucosa
ERBB2	276	ubiquitous	marker	lower esophagus mucosa, right uterine tube, sural nerve
FGFR1	292	ubiquitous	marker	buccal mucosa cell, stromal cell of endometrium, calcaneal tendon
FGFR2	272	broad	marker	C1 segment of cervical spinal cord, spinal cord, corpus callosum
PIK3CA	284	ubiquitous	marker	calcaneal tendon, adrenal tissue, tendon
PSMB8	132	ubiquitous	marker	granulocyte, leukocyte, spleen
PTEN	256	ubiquitous	marker	sperm, endothelial cell, calcaneal tendon
CDH1	245	broad	marker	jejunal mucosa, esophagus squamous epithelium, gingival epithelium
CHD6	251	ubiquitous	marker	sural nerve, calcaneal tendon, endothelial cell
HCN3	132	ubiquitous	marker	cortical plate, right hemisphere of cerebellum, cerebellum
MTX1	134	ubiquitous	marker	right testis, left testis, testis
MUC1	247	ubiquitous	marker	pylorus, pancreatic ductal cell, nasal cavity epithelium
PSCA	133	broad	marker	lower esophagus mucosa, mucosa of stomach, olfactory segment of nasal mucosa

Protein interactions among cohort

Intra-cohort edges: 20.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TP53	22,736
EGFR	18,421
PTEN	11,626
ERBB2	9,659
CDH1	8,738
ATM	7,383
DNMT1	7,179
FGFR1	5,693
PIK3CA	5,157
TYMS	4,628

Intra-cohort edges

A	B	Sources
ATM	TP53	biogrid_interaction, string_interaction
CDH1	EGFR	intact, string_interaction
CDH1	ERBB2	string_interaction
CDH1	FGFR1	biogrid_interaction
CDH1	PTEN	string_interaction
DNMT1	TP53	string_interaction
EGFR	ERBB2	intact, string_interaction
EGFR	HSPH1	intact
EGFR	MUC1	intact
EGFR	PIK3CA	string_interaction
EGFR	PTEN	string_interaction
EIF4EBP1	RICTOR	string_interaction
ERBB2	MUC1	biogrid_interaction
ERBB2	PIK3CA	string_interaction
FGFR1	FGFR2	intact
PBK	PTEN	biogrid_interaction
PBK	TP53	biogrid_interaction, intact
PIK3CA	PTEN	string_interaction
PIK3CA	SLTM	intact
PTEN	TP53	string_interaction

Structural data

PDB: 22 · AlphaFold-only: 2 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
EGFR	P00533	388
TP53	P04637	313
RPS6	P62753	218
PIK3CA	P42336	135
FGFR1	P11362	83
ERBB2	P04626	63
FGFR2	P21802	63
TYMS	P04818	61
CXCR4	P61073	33
DNMT1	P26358	27
EIF4EBP1	Q13541	24
MUC1	P15941	23
PSMB8	P28062	22
CDH1	P12830	22
RICTOR	Q6R327	16
ATM	Q13315	14
PTEN	P60484	12
HCN3	Q9P1Z3	3
HSPH1	Q92598	1
PBK	Q96KB5	1
CHD6	Q8TD26	1
PSCA	O43653	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
MTX1	Q13505	71.83
SLTM	Q9NWH9	52.38

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 371. Enrichment computed across 24 evidence-associated genes (22 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 22 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 Aberrant PI3K in Cancer	5	28.8×	1e-04	EGFR, ERBB2, FGFR1, FGFR2, PIK3CA
PIP3 activates AKT signaling	6	18.2×	1e-04	RICTOR, EGFR, ERBB2, FGFR1, FGFR2, PIK3CA
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	5	22.0×	3e-04	EGFR, ERBB2, FGFR1, FGFR2, PIK3CA
PI3K events in ERBB2 signaling	3	91.6×	3e-04	EGFR, ERBB2, PIK3CA
Signaling by ERBB2 ECD mutants	3	91.6×	3e-04	EGFR, ERBB2, PIK3CA
Developmental Lineage of Mammary Gland Myoepithelial Cells	3	74.2×	5e-04	CDH1, EGFR, ERBB2
Developmental Lineage of Mammary Gland Luminal Epithelial Cells	3	62.3×	7e-04	CDH1, ERBB2, MUC1
Signaling by ERBB2 KD Mutants	3	57.7×	8e-04	EGFR, ERBB2, PIK3CA
PLCG1 events in ERBB2 signaling	2	259.6×	9e-04	EGFR, ERBB2
RAF/MAP kinase cascade	5	13.9×	9e-04	EGFR, ERBB2, FGFR1, FGFR2, PIK3CA
Regulation of TP53 Degradation	3	39.9×	0.002	ATM, TP53, RICTOR
PI3K Cascade	3	37.1×	0.002	FGFR1, FGFR2, PIK3CA
Epithelial-Mesenchymal Transition (EMT) during gastrulation	2	129.8×	0.003	CDH1, FGFR1
TP53 Regulates Transcription of Caspase Activators and Caspases	2	86.5×	0.006	ATM, TP53
ERBB2 Activates PTK6 Signaling	2	74.2×	0.007	EGFR, ERBB2
Stabilization of p53	2	69.2×	0.007	ATM, TP53
TFAP2 (AP-2) family regulates transcription of growth factors and their receptors	2	69.2×	0.007	EGFR, ERBB2
Developmental Lineage of Mammary Stem Cells	2	69.2×	0.007	CDH1, ERBB2
Constitutive Signaling by EGFRvIII	2	64.9×	0.007	EGFR, PIK3CA
ERBB2 Regulates Cell Motility	2	64.9×	0.007	EGFR, ERBB2
Formation of definitive endoderm	2	64.9×	0.007	CDH1, CXCR4
Signaling by ALK fusions and activated point mutants	3	20.5×	0.007	RPS6, TP53, PIK3CA
GAB1 signalosome	2	57.7×	0.008	EGFR, PIK3CA
GRB2 events in ERBB2 signaling	2	57.7×	0.008	EGFR, ERBB2
Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants	2	51.9×	0.010	EGFR, PIK3CA
TP53 Regulates Transcription of Genes Involved in Cytochrome C Release	2	49.4×	0.010	ATM, TP53
Regulation of TP53 Activity through Methylation	2	49.4×	0.010	ATM, TP53
Signal transduction by L1	2	47.2×	0.010	EGFR, FGFR1
PI-3K cascade:FGFR1	2	47.2×	0.010	FGFR1, PIK3CA
PI-3K cascade:FGFR2	2	45.1×	0.011	FGFR2, PIK3CA

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 24 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
fibroblast growth factor receptor signaling pathway involved in orbitofrontal cortex development	2	468.1×	0.002	FGFR1, FGFR2
phosphatidylinositol 3-kinase/protein kinase B signal transduction	4	35.1×	0.002	EGFR, ERBB2, PIK3CA, PTEN
ventricular zone neuroblast division	2	351.1×	0.002	FGFR1, FGFR2
positive regulation of phospholipase activity	2	280.9×	0.003	FGFR1, FGFR2
peptidyl-tyrosine phosphorylation	3	52.7×	0.003	ERBB2, FGFR1, FGFR2
DNA damage response, signal transduction by p53 class mediator	3	44.8×	0.004	ATM, TP53, MUC1
ERBB2-EGFR signaling pathway	2	140.4×	0.006	EGFR, ERBB2
lung-associated mesenchyme development	2	140.4×	0.006	FGFR1, FGFR2
TORC2 signaling	2	127.7×	0.006	RICTOR, PIK3CA
branching involved in salivary gland morphogenesis	2	117.0×	0.006	FGFR1, FGFR2
epidermal growth factor receptor signaling pathway	3	31.0×	0.006	EGFR, ERBB2, PIK3CA
positive regulation of epithelial cell proliferation	3	30.5×	0.006	EGFR, ERBB2, FGFR2
mitotic G1 DNA damage checkpoint signaling	2	87.8×	0.009	TP53, MUC1
positive regulation of MAPK cascade	4	13.4×	0.009	EGFR, ERBB2, FGFR1, FGFR2
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	4	13.1×	0.009	RICTOR, EGFR, FGFR1, PIK3CA
replicative senescence	2	82.6×	0.009	ATM, TP53
positive regulation of cell growth	3	22.9×	0.010	RICTOR, EGFR, ERBB2
TOR signaling	2	63.8×	0.014	RPS6, EIF4EBP1
phosphatidylinositol-mediated signaling	2	58.5×	0.014	FGFR1, PIK3CA
regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	2	58.5×	0.014	RICTOR, PTEN
positive regulation of MAP kinase activity	2	54.0×	0.014	ERBB2, FGFR1
protein autophosphorylation	3	18.2×	0.014	ATM, FGFR1, FGFR2
positive regulation of cell migration	4	10.3×	0.014	ATM, CXCR4, RICTOR, EGFR
cell migration	4	10.2×	0.014	CDH1, FGFR1, PIK3CA, PTEN
positive regulation of cell population proliferation	5	7.0×	0.014	RPS6, EGFR, FGFR1, FGFR2, PTEN
positive regulation of cardiac muscle cell proliferation	2	52.0×	0.014	FGFR1, FGFR2
positive regulation of mesenchymal cell proliferation	2	50.1×	0.014	FGFR1, FGFR2
midbrain development	2	50.1×	0.014	FGFR1, FGFR2
cellular response to gamma radiation	2	50.1×	0.014	ATM, TP53
regulation of ERK1 and ERK2 cascade	2	48.4×	0.014	ERBB2, FGFR2

Therapeutics

Drugs indicated for this disease

4 approved, 23 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Capecitabine	Approved (phase 4)
Ramucirumab	Approved (phase 4)
Tislelizumab	Approved (phase 4)
Trastuzumab	Approved (phase 4)
Albumin Human	Phase 3 (in late-stage trials)
Andecaliximab	Phase 3 (in late-stage trials)
Avelumab	Phase 3 (in late-stage trials)
Bevacizumab	Phase 3 (in late-stage trials)
Camrelizumab	Phase 3 (in late-stage trials)
Catumaxomab	Phase 3 (in late-stage trials)
Cetuximab	Phase 3 (in late-stage trials)
Cisplatin	Phase 3 (in late-stage trials)
Fluorouracil	Phase 3 (in late-stage trials)
Gimeracil	Phase 3 (in late-stage trials)
Ipilimumab	Phase 3 (in late-stage trials)
Irinotecan	Phase 3 (in late-stage trials)
Nivolumab	Phase 3 (in late-stage trials)
Olaparib	Phase 3 (in late-stage trials)
Oteracil	Phase 3 (in late-stage trials)
Oxaliplatin	Phase 3 (in late-stage trials)
Paclitaxel	Phase 3 (in late-stage trials)
Pembrolizumab	Phase 3 (in late-stage trials)
Rivoceranib	Phase 3 (in late-stage trials)
Serplulimab	Phase 3 (in late-stage trials)
Sintilimab	Phase 3 (in late-stage trials)
Sugemalimab	Phase 3 (in late-stage trials)
Tegafur	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Atezolizumab, Cadonilimab, Capivasertib, Dexamethasone, Diphenhydramine, Doxorubicin, Durvalumab, Envafolimab, Famotidine, Floxuridine, Imatinib, Ipatasertib, Lenvatinib, Milademetan, Nintedanib, Panitumumab, Romidepsin, Savolitinib, Selumetinib, Surufatinib, Tipiracil, Toripalimab, Trastuzumab Deruxtecan, Tremelimumab.

Drug target analysis

Approved (phase 4): 13 · Phase ≥3: 14 · Phased (≥1): 15 · Undrugged: 9

Druggability breadth: 23 of 24 evidence-associated genes (96%) 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
ATM	AMIODARONE HYDROCHLORIDE
RPS6	GENTAMICIN SULFATE
TP53	NITROFURANTOIN
TYMS	FOLIC ACID
SLTM	CABOZANTINIB
CXCR4	PLERIXAFOR
DNMT1	DECITABINE
EGFR	LEVODOPA
ERBB2	CLOTRIMAZOLE
FGFR1	PONATINIB
FGFR2	PONATINIB
PIK3CA	IDELALISIB
PSMB8	BORTEZOMIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TP53	196	4
EGFR	175	4
FGFR1	93	4
ERBB2	83	4
PIK3CA	67	4
FGFR2	59	4
ATM	35	4
TYMS	9	4
PSMB8	7	4
DNMT1	6	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
AMIODARONE HYDROCHLORIDE	4	ATM, TP53
FURAZOLIDONE	4	ATM, TP53
ESTRADIOL ACETATE	4	ATM
NAFTIFINE HYDROCHLORIDE	4	ATM
METHYSERGIDE MALEATE	4	ATM
AMITRIPTYLINE HYDROCHLORIDE	4	ATM, TP53
XYLOMETAZOLINE HYDROCHLORIDE	4	ATM
FLUVOXAMINE MALEATE	4	ATM
ESTRADIOL VALERATE	4	ATM
PERMETHRIN	4	ATM
MITOTANE	4	ATM
TICLOPIDINE HYDROCHLORIDE	4	ATM
ENOXIMONE	4	ATM
METHYLENE BLUE ANHYDROUS	4	ATM
DITHIAZANINE IODIDE	4	ATM
ETHACRYNIC ACID	4	ATM, TP53
SECNIDAZOLE	4	ATM
MENADIONE	4	ATM, TP53
FENOFIBRATE	4	ATM
DIPYRIDAMOLE	4	ATM
GENTAMICIN SULFATE	4	RPS6
NITROFURANTOIN	4	TP53
DIOSMIN	4	TP53
VERTEPORFIN	4	TP53
CANDESARTAN CILEXETIL	4	TP53
DIENESTROL	4	TP53
CLOTRIMAZOLE	4	EGFR, ERBB2, TP53
COLCHICINE	4	TP53
NABUMETONE	4	TP53
SALMETEROL XINAFOATE	4	TP53

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 9.

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

Symbol	Assays	Type breakdown
EGFR	6,531	Binding:6211, Functional:173, ADMET:138, Toxicity:9
PIK3CA	2,034	Binding:2009, ADMET:19, Toxicity:4, Functional:2
FGFR1	1,465	Binding:1428, Functional:24, ADMET:13
ERBB2	1,221	Binding:1136, Functional:79, ADMET:6
FGFR2	966	Binding:940, Functional:22, ADMET:4
TP53	869	Binding:775, ADMET:83, Functional:10, Toxicity:1
CXCR4	560	Binding:386, Functional:174
TYMS	376	Binding:373, ADMET:2, Functional:1
PSMB8	262	Binding:250, ADMET:9, Functional:3
ATM	240	Binding:233, Functional:5, ADMET:2
DNMT1	233	Binding:229, Functional:3, ADMET:1
RPS6	108	Binding:108
RICTOR	99	Binding:99
PBK	90	Binding:89, Functional:1
EIF4EBP1	33	Binding:33
HSPH1	18	Binding:14, Functional:4
CDH1	18	Binding:18
SLTM	14	Binding:14
MUC1	13	Binding:13
PTEN	8	Binding:8
HCN3	3	Binding:1, ADMET:1, Functional:1
MTX1	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ATM	2.7.11.1	non-specific serine/threonine protein kinase
TYMS	2.1.1.45	thymidylate synthase
DNMT1	2.1.1.37	DNA (cytosine-5-)-methyltransferase
EGFR	2.7.10.1	receptor protein-tyrosine kinase
ERBB2	2.7.10.1	receptor protein-tyrosine kinase
FGFR1	2.7.10.1	receptor protein-tyrosine kinase
FGFR2	2.7.10.1	receptor protein-tyrosine kinase
PIK3CA	2.7.1.137, 2.7.1.153, 2.7.11.1	phosphatidylinositol 3-kinase, phosphatidylinositol-4,5-bisphosphate 3-kinase, non-specific serine/threonine protein kinase
PTEN	3.1.3.16, 3.1.3.67	protein-serine/threonine phosphatase, phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
ATM	240
RPS6	108
TP53	869
TYMS	376
CXCR4	560
DNMT1	233
EGFR	6,531
ERBB2	1,221
FGFR1	1,465
FGFR2	966
PIK3CA	2,034
PSMB8	262

Pharmacogenomics

Cohort genes with a PharmGKB record: 24; 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)
AMIODARONE HYDROCHLORIDE	4	ATM, TP53
FURAZOLIDONE	4	ATM, TP53
ESTRADIOL ACETATE	4	ATM
NAFTIFINE HYDROCHLORIDE	4	ATM
METHYSERGIDE MALEATE	4	ATM
AMITRIPTYLINE HYDROCHLORIDE	4	ATM, TP53
XYLOMETAZOLINE HYDROCHLORIDE	4	ATM
FLUVOXAMINE MALEATE	4	ATM
ESTRADIOL VALERATE	4	ATM
PERMETHRIN	4	ATM
MITOTANE	4	ATM
TICLOPIDINE HYDROCHLORIDE	4	ATM
ENOXIMONE	4	ATM
METHYLENE BLUE ANHYDROUS	4	ATM
DITHIAZANINE IODIDE	4	ATM
ETHACRYNIC ACID	4	ATM, TP53
SECNIDAZOLE	4	ATM
MENADIONE	4	ATM, TP53
FENOFIBRATE	4	ATM
DIPYRIDAMOLE	4	ATM
GENTAMICIN SULFATE	4	RPS6
NITROFURANTOIN	4	TP53
DIOSMIN	4	TP53
VERTEPORFIN	4	TP53
CANDESARTAN CILEXETIL	4	TP53
DIENESTROL	4	TP53
CLOTRIMAZOLE	4	EGFR, ERBB2, TP53
COLCHICINE	4	TP53
NABUMETONE	4	TP53
SALMETEROL XINAFOATE	4	TP53

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	13	ATM, RPS6, TP53, TYMS, SLTM, CXCR4, DNMT1, EGFR, ERBB2, FGFR1 (+3 more)
B	Phased (≥1) drug, not yet approved	2	PBK, RICTOR
C	Druggable family + PDB, no drug	2	PTEN, HCN3
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	7	HSPH1, EIF4EBP1, CDH1, CHD6, MTX1, MUC1, PSCA

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
PTEN	8	TP53
CDH1	18	EGFR
MUC1	13	EGFR
HSPH1	18	—
EIF4EBP1	33	—
CHD6	0	—
HCN3	3	—
MTX1	1	—
PSCA	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 365.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	165
Not specified	69
PHASE1	49
PHASE1/PHASE2	32
PHASE3	30
PHASE2/PHASE3	9
EARLY_PHASE1	7
PHASE4	4

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00844675	PHASE4	COMPLETED	Effects of Oral Rabeprazole on the Prevention of Ulcer Bleeding Following Endoscopic Mucosal Resection
NCT00871273	PHASE4	TERMINATED	Pharmacokinetic Study of Capecitabine After Total Gastrectomy for Stomach Adenocarcinoma
NCT02366819	PHASE4	SUSPENDED	Genetic Analysis-Guided Irinotecan Hydrochloride Dosing of mFOLFIRINOX in Treating Patients With Locally Advanced Gastroesophageal or Stomach Cancer
NCT06192186	PHASE4	UNKNOWN	Adebrelimab Combined With SOX Regimen in Preoperative Neoadjuvant Transformation Therapy for Locally Advanced Gastric Adenocarcinoma
NCT01882933	PHASE3	ACTIVE_NOT_RECRUITING	D2 Resection and HIPEC (Hyperthermic Intraperitoneal Chemoperfusion) in Locally Advanced Gastric Carcinoma
NCT04248452	PHASE3	ACTIVE_NOT_RECRUITING	Testing the Addition of Radiotherapy to the Usual Treatment (Chemotherapy) for Patients With Esophageal and Gastric Cancer That Has Spread to a Limited Number of Other Places in the Body
NCT05002127	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	A Study of Evorpacept (ALX148) in Patients With Advanced HER2+ Gastric Cancer (ASPEN-06)
NCT05482516	PHASE3	RECRUITING	Evaluating Novel Therapies in ctDNA Positive GI Cancers
NCT05677490	PHASE3	RECRUITING	mFOLFIRINOX Versus mFOLFOX With or Without Nivolumab for the Treatment of Advanced, Unresectable, or Metastatic HER2 Negative Esophageal, Gastroesophageal Junction, and Gastric Adenocarcinoma
NCT05813015	PHASE3	RECRUITING	Study of Comparing of With and Without Sequential Therapy of S-1
NCT06028737	PHASE2/PHASE3	RECRUITING	Total Neoadjuvant FLOT Chemotherapy in Locally Advanced Gastric and Gastroesophageal Junction Cancer
NCT06203600	PHASE2/PHASE3	RECRUITING	Adding Nivolumab to Usual Treatment for People With Advanced Stomach or Esophageal Cancer, PARAMUNE Trial
NCT06206733	PHASE3	ACTIVE_NOT_RECRUITING	ASKB589 in Combination With CAPOX and PD-1 Inhibitor in Patients With Advanced or Metastatic GC/GEJ Adenocarcinoma
NCT07000253	PHASE2/PHASE3	RECRUITING	Timing of Minimally Invasive Local Treatment After First-Line Systemic Therapy in Oligometastatic Esophageal or Gastric Adenocarcinoma
NCT07001748	PHASE2/PHASE3	RECRUITING	Testing the Addition of Paclitaxel Administered Into the Abdominal Cavity Combined With Chemotherapy for Patients With Gastric Cancer Spread to the Abdominal Cavity
NCT07018661	PHASE2/PHASE3	RECRUITING	[18F]F-FAPI PET/CT and Laparoscopy in Staging Advanced Gastric Cancer
NCT07029269	PHASE3	RECRUITING	Feasibility of Enhanced Recovery After Surgery Without Prophylactic Abdominal Drainage Tubes After Laparoscopic Distal Gastrectomy For Gastric Cancer
NCT07043400	PHASE3	RECRUITING	A Study to Investigate Tislelizumab Administered as Subcutaneous Injection Versus Intravenous Infusion Plus Chemotherapy in Patients With Unresectable or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma
NCT07103668	PHASE3	RECRUITING	A Phase III Randomized Study in CLDN18.2-positive Unresectable Locally Advanced Gastric Cancer Patients
NCT07152405	PHASE3	RECRUITING	A Study of BL-M07D1 Versus Investigator’s Choice of Chemotherapy in Patients With HER2-positive Locally Advanced or Metastatic Gastric or Gastro-esophageal Junction Adenocarcinoma
NCT07584135	PHASE3	NOT_YET_RECRUITING	JS107 in Combination With Toripalimab and Chemotherapy for the Treatment of CLDN18.2-positive Gastric or Gastroesophageal Junction Adenocarcinoma
NCT07603349	PHASE2/PHASE3	NOT_YET_RECRUITING	Adaptive Adjuvant Therapy After Neoadjuvant Therapy and Gastrectomy for Gastric or Gastroesophageal Junction Adenocarcinoma
NCT01283217	PHASE3	UNKNOWN	Docetaxel and S1 (DS) Versus S1 and Cisplatin (SP) in Curatively Resected Stage IIIB/IV Gastric Cancer
NCT01583361	PHASE3	UNKNOWN	SOX Regimen as Neoadjuvant Chemotherapy for AJCC Stage II-III Gastric Cancer
NCT01640782	PHASE3	COMPLETED	Intergroup Trial of Adjuvant Chemotherapy in Adenocarcinoma of the Stomach
NCT01989858	PHASE3	TERMINATED	ITACA-S2 (Intergroup Trial in Adjuvant Chemotherapy for Adenocarcinoma of the Stomach)
NCT02144727	PHASE3	UNKNOWN	A Clinical Trial of D1+ Versus D2 Distal Gastrectomy for Stage IB & II Advanced Gastric Cancer
NCT02240524	PHASE3	UNKNOWN	Efficacy of HIPEC in the Treatment of Patients With Locally Advanced Gastric Cancer
NCT02314117	PHASE3	COMPLETED	A Study of Ramucirumab (LY3009806) in Combination With Capecitabine and Cisplatin in Participants With Stomach Cancer
NCT02370498	PHASE3	COMPLETED	A Study of Pembrolizumab (MK-3475) Versus Paclitaxel for Participants With Advanced Gastric/Gastroesophageal Junction Adenocarcinoma That Progressed After Therapy With Platinum and Fluoropyrimidine (MK-3475-061/KEYNOTE-061)
NCT02494583	PHASE3	COMPLETED	Study of Pembrolizumab (MK-3475) as First-Line Monotherapy and Combination Therapy for Treatment of Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (MK-3475-062/KEYNOTE-062)
NCT02512380	PHASE3	UNKNOWN	Neoadjuvant SLOT Versus SOX in Patients With Locally Advanced, Resectable Gastric/Esophagogastric Junction (EGJ) Cancer
NCT02545504	PHASE3	COMPLETED	Andecaliximab With mFOLFOX6 as First Line Treatment for Advanced Gastric or Gastroesophageal Junction Adenocarcinoma
NCT02898077	PHASE3	COMPLETED	A Study of Paclitaxel With or Without Ramucirumab (LY3009806) in Participants With Gastric or Gastroesophageal Cancer
NCT03042169	PHASE3	TERMINATED	Surgical Resection Plus Chemotherapy Versus Chemotherapy Alone in Oligometastatic Stage IV Gastric Cancer
NCT03042611	PHASE3	COMPLETED	A Study to Evaluate Rivoceranib Plus Best Supportive Care Compared to Placebo Plus Best Supportive Care in Participants With Gastric Cancer
NCT03691454	PHASE2/PHASE3	UNKNOWN	Compare Neoadjuvant Chemotherapy of DOS Versus SOX in Locally Advanced Gastric Adenocarcinoma.
NCT03802591	PHASE3	COMPLETED	A Study of CS1001 in Subjects With Gastric Adenocarcinoma or Gastro-Esophageal Junction Adenocarcinoma
NCT03973008	PHASE3	UNKNOWN	Adujvant CT+CRT vs Adujvant CT After D2 Resection for Locally Advanced Proximal Gastric Adenocarcinoma
NCT04499924	PHASE2/PHASE3	COMPLETED	Tucatinib, Trastuzumab, Ramucirumab, and Paclitaxel Versus Paclitaxel and Ramucirumab in Previously Treated HER2+ Gastroesophageal Cancer

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
RAMUCIRUMAB	4	18
IRINOTECAN	4	7
TIPIRACIL	4	6
INDOCYANINE GREEN ACID FORM	4	4
TRIFLURIDINE	4	4
DOSTARLIMAB	4	3
LEUCOVORIN	4	3
TISLELIZUMAB	4	3
CATUMAXOMAB	4	2
FLOXURIDINE	4	2
FLUDEOXYGLUCOSE F 18	4	2
NIRAPARIB	4	2
PEMBROLIZUMAB	4	2
TUCATINIB	4	2
AVELUMAB	4	1
CABAZITAXEL	4	1
CAPECITABINE	4	1
CAPIVASERTIB	4	1
CAPMATINIB	4	1
CERITINIB	4	1
COBIMETINIB	4	1
DIPHENHYDRAMINE	4	1
FAMOTIDINE	4	1
FLUDARABINE PHOSPHATE	4	1
FLUOROURACIL	4	1
FRUQUINTINIB	4	1
FUTIBATINIB	4	1
LINAGLIPTIN	4	1
OXALIPLATIN	4	1
PANITUMUMAB	4	1

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 20 predictive associations from 21 curated evidence items; also 5 prognostic, 1 oncogenic.

Molecular subtype	Therapy	Effect	Level	CIViC
ERBB2 Amplification	Trastuzumab	Sensitivity/Response	CIViC A	EID1499 +1
CLDN18 positive	FOLFOX-6 Regimen + Zolbetuximab	Sensitivity/Response	CIViC A	EID12215
CLDN18 positive	CAPOX Regimen + Zolbetuximab	Sensitivity/Response	CIViC A	EID12216
EGFR Amplification	Cetuximab	Sensitivity/Response	CIViC B	EID6927
ERBB2 Amplification	Lapatinib	Sensitivity/Response	CIViC B	EID1023
TP53 Mutation	Chemotherapy	Sensitivity/Response	CIViC B	EID850
CXCR4 EXPRESSION	Docetaxel	Resistance	CIViC B	EID949
DNMT1 EXPRESSION	Cisplatin	Resistance	CIViC B	EID946
PTEN Loss	Trastuzumab + Lapatinib	Resistance	CIViC B	EID864
TYMS Overexpression	Raltitrexed	Resistance	CIViC B	EID929
FGFR2 Amplification	Futibatinib	Sensitivity/Response	CIViC C	EID11637
FGFR3::TACC3 Fusion	Futibatinib	Sensitivity/Response	CIViC C	EID11638
MET Amplification	Onartuzumab	Sensitivity/Response	CIViC C	EID689
ATM Underexpression	Olaparib	Sensitivity/Response	CIViC D	EID878
EIF4EBP1 PHOSPHORYLATION	Everolimus	Sensitivity/Response	CIViC D	EID918
FGFR1 Expression	Infigratinib	Sensitivity/Response	CIViC D	EID800
HSPH1 NUCLEAR EXPRESSION	Fluorouracil + Cisplatin	Sensitivity/Response	CIViC D	EID1163
MET Amplification	Cabozantinib	Sensitivity/Response	CIViC D	EID7873
RICTOR Amplification	Vistusertib	Sensitivity/Response	CIViC D	EID1915
RPS6 PHOSPHORYLATION	Everolimus	Sensitivity/Response	CIViC D	EID930