2-methoxyestradiol + bevacizumab

2-methoxyestradiol + bevacizumab is an investigational combination therapy consisting of 2-methoxyestradiol (2ME2), a natural estradiol metabolite with anti-angiogenic and antiproliferative properties, and bevacizumab, a recombinant humanized monoclonal antibody against vascular endothelial growth factor A (VEGF-A). 2ME2 acts primarily by disrupting microtubule function and inhibiting hypoxia-inducible factor 1-alpha (HIF-1α), thus reducing angiogenesis and tumor cell proliferation. Bevacizumab binds and neutralizes VEGF-A, preventing its interaction with VEGF receptors on endothelial cells and thereby suppressing tumor neovascularization. The combination leverages dual anti-angiogenic mechanisms for potential synergistic antitumor effects. It has been studied in phase II trials for advanced carcinoid tumors, with evidence supporting safety and modest antitumor activity, though no major tumor regression was observed[1][3][7].