Synergistic anti-tumor effects of novel two-domain soluble Fms-like tyrosine kinase-1 and paclitaxel on three-dimensional breast cancer models: implications for targeted therapy

2d-sFlt-1 enhanced paclitaxel efficacy in physiologically relevant 3D breast cancer models. In MDA-MB-231 spheroids, the combination reduced chemoresistance and invasive growth through coordinated modulation of angiogenesis, EMT, and FAK signaling. In MDA-MB-468 and MCF-7 spheroids, it primarily increased cytotoxicity and growth inhibition, indicating a conserved functional benefit across subtypes. These findings provide a rationale for further mechanistic validation and preclinical evaluation of 2d-sFlt-1 plus paclitaxel to define dosing, safety, and translational feasibility in aggressive breast cancers.