Advances in PROTACs Promote the Development of Anticancer Therapy

Protein, as one of the key components of living organisms, performs most of the functions necessary for life. Protein dysfunction is usually associated with numerous diseases, such as cancer and age-related diseases. Targeted protein degradation by proteolysis-targeting chimera (PROTAC), as an emerging therapeutic modality, has attracted increasing interest in chemotherapy. PROTACs contain two ligands and a chemical linker to connect them. The ligands binding to a target protein and an E3 ubiquitin ligase respectively, thereby, promotes ubiquitination and degradation of pathogenic proteins via the ubiquitin-proteasome system. In this way, previously “undruggable” proteins become druggable, providing an alternative strategy for anti-tumor therapy. Yet, challenges associated with PROTACs are still present, including poor in vivo bioavailability and potential off-target toxicity. Developing novel PROTACs to target disease-specific proteins and inducible precursors to reduce off-target effects promotes their progress from academia to industry, which will ultimately benefit clinical patients.

This topic invites submissions of original research articles and comprehensive reviews, which facilitate our understanding of targeted protein degradation and the development of PROTACs. Furthermore, innovative strategies to reduce off-target or adverse effects of PROTACs are highly encouraged. This Research Topic will explore various aspects related to PROTACs. Subtopics may include but are not limited to:

• Novel PROTACs for antitumor therapy;

• Mechanistic investigation on targeted protein degradation;

• Exploration of strategies to reduce adverse effects of PROTACs.