Table 2

Summary of selected novel biomarkers for gastric cancer

Biomarkers	Key preclinical evidence	Targeted therapy in clinical trials
DKK1	Promotes epithelial-to-mesenchymal transition and contributes to cisplatin resistance⁹³ Promotes tumor immune invasion and impede anti-PD-1 treatment⁹⁴ DKK1 blockade reduced the growth of human gastric cancer tumors with high DKK1 expression in a xenograft model⁹⁴	DKN-01 Well-tolerated in phase Ib and IIa trials^95,96 Phase II trial ongoing (NCT04363801)⁹⁶
VISTA	Expression associated with PD-L1 expression⁹⁷ Predominantly expressed on tumor-associated macrophages in gastric cancer⁹⁸ VISTA blockade promoted T cell-medicated antitumor immunity and enhanced the efficacy of PD-1 inhibitor in ex vivo tumor inhibition assay⁹⁸	SNS-101 Phase I/II study ongoing (NCT05864144)⁹⁹
B7-H3	High level associated with low intra-tumoral CD8⁺ T cell density¹⁰⁰ Promotes stemness characteristics to gastric cancer cells by promoting glutathione metabolism¹⁰¹ B7-H3-directed CAR-T cells showed anti-tumor effect in xenograft model¹⁰²	None identified
Aquaporin-5	Specifically highly expressed by gastric cancer stem cells¹⁰³ Coordinates with LGR5 to determine the fates of gastric cancer stem cells¹⁰³ Overexpression associated with lymph node metastasis¹⁰⁴	None identified

CAR-T cells, chimeric antigen receptor T cells; DKK1, dickkopf-1; LGR5, leucine-rich repeat-containing G protein-coupled receptor 5; PD-1, programmed death-1; PD-L1, programmed death-ligand 1; VISTA, V-domain immunoglobulin-containing suppressor of T-cell activation.