Proteolysis-Targeting Chimeras in Cancer Therapy: Targeted Protein Degradation for Next-Generation Treatment

Proteolysis-targeting chimeras (PROTACs) offer a groundbreaking approach to cancer therapy by enabling the targeted degradation of oncogenic proteins, including those previously considered "undruggable." By utilizing the ubiquitin-proteasome system, PROTACs achieve sustained protein suppression with lower doses and reduced toxicity compared to traditional inhibitors. Their bifunctional design facilitates the selective ubiquitination and degradation of disease-causing proteins, showing promise in treating both solid and hematologic cancers. Several PROTAC candidates are progressing to clinical trials, highlighting their potential to overcome drug resistance and expand cancer treatment options. Despite their promise, challenges remain in optimizing PROTACs, particularly regarding pharmacokinetics, E3 ligase compatibility, and effective tumor delivery. Overall, PROTACs represent a versatile and precise platform for personalized cancer therapy.