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: In vitro assays including CellTiter-Glo cell viability, tube formation, transwell and chemotaxis migration were conducted to evaluate PB101's effects on cell survival, migration, and endothelial angiogenesis. An in vivo NCI-N87 xenograft model was used to evaluate antitumor efficacy. Tumor angiogenesis was assessed by CD31 immunohistochemistry.

RESULTS: PB101 exerted no direct cytotoxicity on GC cells, either alone or in combination with chemotherapy. However, it demonstrated potent anti-angiogenic properties by significantly inhibiting endothelial cell migration and tube formation. As 2D culture cannot recapitulate the tumor microenvironment (TME), in vivo studies were conducted. In vivo 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.