Review on PROTACs as Precision Medicine: Targeted Protein Degradation in Oncology

Abstract

Proteolysis-targeting chimeras (PROTACs) have emerged as a revolutionary class of small molecules in the field of precision medicine, offering a novel approach to targeted protein degradation in oncology. Unlike traditional inhibitors that merely block the function of diseaserelated proteins, PROTACs harness the cell's natural degradation machinery to selectively eliminate pathogenic proteins. This review explores the fundamental principles of PROTAC technology, its development, and its application in cancer therapy. We discuss the design and mechanism of action of PROTACs, highlighting their ability to target previously "undruggable" proteins. The review also covers the latest advancements in PROTAC-mediated degradation of oncogenic drivers, resistance mechanisms, and strategies to overcome these challenges. Additionally, we examine the preclinical and clinical progress of PROTACs in oncology, emphasizing their potential to transform cancer treatment by offering improved specificity, efficacy, and reduced off-target effects. Through a comprehensive analysis of current research, this paper underscores the promise of PROTACs as a paradigm shift in the development of precision oncology therapeutics.