Proteolysis targeting chimeras (PROTACs) in oncology: a review of patents and regulatory considerations

Proteolysis Targeting Chimeras (PROTACs) represents a groundbreaking advancement in drug discovery and targeted protein degradation. Unlike traditional small-molecule inhibitors, PROTACs leverage the cell's natural protein degradation machinery to selectively degrade pathogenic proteins, offering significant therapeutic potential for previously undruggable targets and complex diseases such as cancer and neurodegenerative disorders. Understanding the regulatory landscape governing their approval is crucial as their development accelerates. This review provides an overview of recent patents, regulatory considerations, emerging concerns, and future perspectives of PROTACs in cancer management. From a regulatory perspective, PROTACs present unique challenges and opportunities. Their dual-functional nature requires a nuanced approach to classification and approval, blending small-molecule and biologic regulatory frameworks. Specific guidelines addressing pharmacokinetic and pharmacodynamic profiles are needed. Comprehensive preclinical evaluation and robust clinical trial designs are essential to manage off-target effects and immunogenic responses. The collaboration between regulatory bodies, academia, and industry is crucial for establishing a clear pathway for PROTAC approval. Future considerations must account for advancements in PROTAC technology to ensure safe and effective therapies reach patients. While PROTACs hold immense promise, their regulatory journey requires tailored guidelines and rigorous evaluation to realize their full potential.