Dimer peptide D6 slows human gastric tumor progression in mouse xenografts, matching bevacizumab activity

Gastric cancer (GC) remains a major global health problem, often diagnosed at late stages with high mortality. Current therapeutic strategies, including anti-angiogenic agents targeting Vascular Endothelial Growth Factor (VEGF), are used in combination therapies but offer modest efficacy. A key limitation of existing anti-VEGF antibodies, like bevacizumab, is their large size, which can hinder tissue penetration into solid tumors. This creates a critical gap for developing smaller, more permeable agents that can effectively reach and inhibit tumor angiogenesis.

Researchers evaluated the efficacy of D6, a previously identified dimer peptide ligand of VEGF, in both in vitro and in vivo models. For in vitro studies, human gastric cancer cells were treated with D6 to assess proliferation inhibition. For in vivo assessment, a murine xenograft model was established using human gastric tumor cells. Mice bearing these xenografts were treated with D6 via repeated injections, and its activity was compared against bevacizumab, a standard anti-VEGF antibody, which served as the positive control. The primary endpoint was the inhibition of tumor growth.

The dimer peptide D6 demonstrated significant activity in inhibiting the proliferation of gastric cancer cells in vitro. More critically, in the murine xenograft model, D6 effectively slowed the progression of human gastric tumors. > The activity of the D6 peptide in these assays was comparable to that of bevacizumab, the established anti-VEGF antibody used as a positive control. This comparable efficacy was observed across both in vitro cell proliferation and in vivo tumor growth inhibition models. However, the peptide required repeated injections at higher molar concentrations to achieve this level of activity, suggesting differences in pharmacokinetics or potency compared to the antibody.