Dose- and strategy-dependent effects of anti-angiogenic therapy on tumor growth and microenvironment remodeling

To investigate how anti-angiogenic therapies influence tumor growth and tumor microenvironment remodeling in colorectal cancer, and to evaluate treatment-associated differences across dosages, therapeutic agents, and combination strategies. A murine colorectal cancer model established with MC38 cells was used to compare anti-angiogenic treatments across different doses, therapeutic agents, and combination regimens. Tumor growth was monitored, and microenvironmental changes were assessed using hematoxylin and eosin staining, reticulin staining, immunohistochemistry, and ELISA to characterize vascular, stromal, immune, and inflammatory alterations. All anti-angiogenic treatments inhibited tumor growth, with combination regimens showing greater efficacy than monotherapy. Fruquintinib exhibited a clear dose-dependent effect. Distinct treatment-associated remodeling patterns were observed, with bevacizumab associated with relatively organized vascular and stromal features, while the tested small-molecule TKIs were associated with more heterogeneous structural alterations. The low-dose combination strategy promoted coordinated vascular and immune microenvironment remodeling while maintaining antitumor activity. Anti-angiogenic treatments produced distinct tumor microenvironment remodeling patterns, with treatment-dependent changes in vascular and stromal organization. Optimizing dosing and combination strategies may help balance antitumor activity with coordinated microenvironmental remodeling. These findings provide a basis for further evaluation of anti-angiogenic strategies across additional colorectal cancer models.