CD44 and colorectal cancer: 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.