Immunotherapy for advanced gastric cancer

Table 1 The Cancer Genome Atlas has presented a thorough depiction of the molecular basis of gastric cancer[25]

Subtypes	EBV-positive	MSI	GS	CIN
Frequency, %	8.8	21.7	19.7	449.8
Demographic	Male patients (81%)	Old age (median 72 yr)	Young age (median 59 yr)	Not specific
Histology	Not specific	Not specific	Diffuse	Intestinal
Main location	Fundus and body	Fundus, body, and antrum	Mostly diffuse subtype	Majority of tumors at the GEJ
Molecular	EBV-CIMP: (1) PD-L1/2, JAK2 overexpression; (2) Mutation in PIK3CA, ARID1A, and BCOR; (3) CDKN2A silencing; (4) Immune cell signaling; and (5) Rare TP53 mutations	Gastric-CIMP: (1) Hypermutation in TP53, PIK3CA, ERBB2/3, and ARID1A; (2) MLH1 silencing; (3) Mitotic pathways activation; and (4) Commune changes in the genes of CMH1	(1) CDH1 and RHOA mutation; (2) CLDN18-ARHGAP fusion; (3) Cell adhesion; (4) Angiogenesis pathways enriched; and (5) Rare TP53 mutations	(1) TP53 mutation; (2) RTK-RAS activation; and (3) Mutations of SMAD4 and APC
alterations
Potential therapeutic points	(1) PIK3CA; (2) JAK2; and (3) PD-L1/L2	(1) PIK3CA; (2) ERBB2/3; (3) EGFR; (4) PD-L1; and (5) MLH1 silencing	(1) RHOA; and (2) CLDN18	(1) RTKs; (2) EGFR; (3) VEGFA; (4) CCNE1; (5) CCND1; and (6) CDK6

APC: Adenomatous polyposis coli; ARHGAP: Rho GTPase activating protein; ARID1A: AT-rich interactive domain-containing protein 1A; BCOR: B-cell lymphoma 6 corepressor; CCND1: Cyclin-D1; CCNE1: Cyclin-E1; CDH1: Cadherin 1; CDK6: Cyclin-dependent kinase 6; CDKN2A: Cyclin-dependent kinase inhibitor 2A; CIMP: CpG island methylator phenotype; CIN: Chromosomal instability; CLDN18: Claudin-18; CMH1: Hypertrophic cardiomyopathy-1; GS: Genomically stable; GC: Gastric cancer; EBV: Epstein-Barr virus; EGFR: Epithelial growth factor receptor; ERBB2/3: Erb-b2 receptor tyrosine kinase 2/3; GEJ: Gastroesophageal junction; JAK2: Janus-associated kinase 2; MLH1: MutL protein homolog 1; MSI: Microsatellite instability; PD-L1/2: Programmed death ligand-1/2; PI3K: Phosphatidylinositol-3-kinase; RAS: Rat sarcoma virus; RHOA: Ras homolog family member A; RTKs: Receptor tyrosine kinases; SMAD4: Mothers against decapentaplegic homolog 4; TP53: Tumor protein 53; VEGFA: Vascular endothelial growth factor A.