EVs from CAFs of hormone therapy-resistant breast cancer patients promote estrogen receptor-independent oxidative phosphorylation and hormone therapy resistance.574 Furthermore, CAFs create a resistant niche through close interactions with CSCs, secreting factors like IL-6 and IL-8 that support CSC survival.575 In colorectal cancer, CAF-derived EVs trigger resistance to 5-fluorouracil in CSCs, which is the standard of care.576 Endothelial cells can promote resistance in GSCs through the secretion of NO, enhancing Notch signaling, or by releasing CD44 ligands. This evidence concerns the gene CD44 and breast cancer.