Other therapeutic peptides
A wide range of therapeutic peptides showed potential effects on various diseases 5, 133, and some of them were investigated using organoid systems. For example, the two Axin-derived staple peptides SAHPA1 and xStAx that target β-catenin were reported to promote the activity of Wnt/β-catenin signaling pathway134. The investigation of patient-derived tumor organoids showed that xStAx binds to the VHL ligand to promote intestinal tumor death, highlighting its potential as a novel anti-cancer drug.
Leucine-rich-repeat-containing G-protein-coupled receptor 5 (LGR5) positive intestinal adult stem cells are widely used to generate intestinal organoids. The culture technique is mature, and the derived organoids can undergo long-term expansion without changing the genetic features135, 136. The Frizzled 7 receptors (FZD7) are highly expressed in LGR5+ intestinal stem cells and are critical in regulating self-renewal. The development of targeted drugs that bind to FZD7 is a potential approach to investigating FZD7 functions in cancer biology and developing novel regenerative therapy for intestinal epithelium. Nile et al. identified a potent peptide (dFz7-21) that specifically targets FZD7 and changes the conformation of the FZD domain137. The treatment of LGR5+ mice intestinal stem cells derived organoids with FZD7 suppressed stem cell function and disrupted the bud formation by impairing Wnt signaling, proving the utility and feasibility of organoids as preclinical models.