Recent Therapeutic Approaches to Modulate the Hippo Pathway in Oncology and Regenerative Medicine

Area of Science:

• Oncology
• Molecular Biology
• Cell Signaling

Background:

• The Hippo pathway is a conserved signaling network regulating organ size, proliferation, and apoptosis.
• Dysregulation of the Hippo pathway is implicated in solid tumors, contributing to hyperproliferation and immune evasion.
• YAP1/TAZ and TEAD transcription factors are key effectors of the Hippo pathway with therapeutic potential.

Purpose of the Study:

• To review current strategies for targeting the YAP1/TAZ-TEAD protein-protein interaction (PPI).
• To highlight recent advancements in small molecules that inhibit YAP1/TAZ-TEAD-dependent transcription in cancer.

Main Methods:

• Review of recent literature on Hippo pathway targeting strategies.
• Focus on small molecules that bind to TEAD and inhibit YAP1/TAZ-TEAD transcriptional activity.
• Discussion of targeting YAP1/TAZ-TEAD protein-protein interactions (PPIs).

Main Results:

• YAP1/TAZ and TEAD1-4 are crucial for Hippo pathway signaling in cancer.
• Small molecules targeting TEAD, including those blocking autopalmitoylation, show promise.
• Inhibiting YAP1/TAZ-TEAD interactions offers a therapeutic strategy for various cancers.

Conclusions:

• Targeting the YAP1/TAZ-TEAD axis presents a promising therapeutic avenue in oncology.
• Modulating Hippo pathway biology offers potential in cancer, inflammation, and regenerative medicine.
• Recent small molecule inhibitors provide new strategies to disrupt YAP1/TAZ-TEAD transcriptional activity.