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.