Therapeutic Efficacy of PB101 and Chemotherapy Combination in Preclinical Gastric Cancer Models.

BACKGROUND/AIM: Gastric cancer (GC) remains a leading cause of cancer-associated deaths globally, particularly in East Asia. Although anti-angiogenic therapies have yielded therapeutic benefit in GC, their efficacy is limited, as current vascular endothelial growth factor-A (VEGF-A) and VEGF receptor-2 (VEGFR-2) targeted therapies eventually fail due to compensatory pathways involving VEGF-B and placental growth factor (PlGF). PB101, a VEGFR-1 decoy receptor, inhibits VEGF-A, VEGF-B, and PlGF, potentially offering broader anti-angiogenic effects. This study evaluated the efficacy of PB101 alone and in combination with cytotoxic chemotherapeutic agents in GC models. MATERIALS AND METHODS: NCI-N87 xenograft model was used to evaluate antitumor efficacy. Tumor angiogenesis was assessed by CD31 immunohistochemistry. RESULTS: studies revealed that mice receiving PB101 plus paclitaxel or irinotecan exhibited greater tumor volume suppression compared to each single-agent treatment group. Harvested tumors from PB101 and combination groups showed reduced CD31 expression, indicating reduced angiogenesis. CONCLUSION: PB101, blocking VEGF-A/B and PlGF, showed broad anti-angiogenic activity and enhanced chemotherapy efficacy in GC xenograft models when used in combination.