A study led by Wang and colleagues reports a ferroptosis-based nanotherapy that selectively targets colorectal cancer‑associated fibroblasts (CAFs), reversing their tumor-supportive phenotype and remodeling the tumor microenvironment. The nanoparticle approach induces iron‑dependent lipid peroxidation in CAFs, reducing desmoplasia and improving anti-tumor efficacy in preclinical models. Ferroptosis is a regulated, iron‑dependent form of cell death; targeting non‑malignant stromal cells to sensitize tumors is an emerging strategy. Translational hurdles include delivery specificity, off-target ferroptosis risk, and demonstration of synergy with existing immuno- or chemotherapy regimens.