Advancing human epidermal growth factor receptor 2-positive gastric cancer therapy: Toward targeted immunotherapy and antibody-drug conjugates

Figure 2 Resistance mechanisms to targeted and antibody-drug conjugate therapy in human epidermal growth factor receptor 2-positive gastric cancer a visual summary of the diverse mechanisms underlying treatment resistance. (1) Human epidermal growth factor receptor 2 gene mutations and structural alterations; (2) Impaired drug transport; (3) Lysosomal dysfunction; (4) Payload-related drug resistance; (5) Cell survival related mechanisms; (6) Tumor microenvironment remodeling; (7) Bypass signaling activation; (8) Aberrant downstream pathway activation; and (9) Tumor heterogeneity. HER2: Human epidermal growth factor receptor 2; IHC: Immunohistochemistry; ISH: In situ hybridization; ctDNA: Circulating tumor DNA; CTC: Circulating tumor cell; IO: Immunotherapy; T-DXd: Trastuzumab deruxtecan; RC48: Disitamab vedotin; ADC: Antibody-drug conjugate; CAR-T: Chimeric antigen receptor T-cell immunotherapy; TTC: Targeted thorium conjugate.