Targeted Protein Degradation Of Wnt/β-Catenin Signaling Pathway: An Effective Strategy For Cancer Therapy

The document reviews the challenges and potential strategies for targeting the Wnt/β-catenin signaling pathway in cancer therapy. This pathway is crucial for normal cellular functions but is also implicated in cancer progression, making it a difficult target due to its "undruggable" nature. Traditional inhibitors face issues like toxicity and lack of distinct binding sites. Targeted protein degradation (TPD) technologies, such as PROTACs and LYTACs, offer a promising alternative by degrading key proteins in the pathway, potentially overcoming drug resistance and minimizing side effects. The review emphasizes the need for tumor-specific targeting to avoid adverse effects on healthy tissues and suggests combining Wnt inhibitors with immunotherapy to enhance anti-tumor responses. Despite challenges like improving delivery efficiency and managing toxicity, TPD approaches could significantly advance cancer treatment by effectively targeting the Wnt pathway.