Protacs in cancer therapy: mechanisms, design, clinical trials, and future directions

Cancer develops as a result of changes in both genetic and epigenetic mechanisms, which lead to the activation of oncogenes and the suppression of tumor suppressor genes. Despite advancements in cancer treatments, the primary approach still involves a combination of chemotherapy, radiotherapy, and surgery, typically providing a median survival of approximately five years for patients. Unfortunately, these therapeutic interventions often bring about substantial side effects and toxicities, significantly impacting the overall quality of life for individuals undergoing treatment. Therefore, urgent need of research required which comes up with effective treatment of cancer. This review explores the transformative role of Proteolysis-Targeting Chimeras (PROTACs) in cancer therapy. PROTACs, an innovative drug development strategy, utilize the cell's protein degradation machinery to selectively eliminate disease-causing proteins. The review covers the historical background, mechanism of action, design, and structure of PROTACs, emphasizing their precision in targeting oncogenic proteins. The discussion extends to the challenges, nanotechnology applications, and ongoing clinical trials, showcasing promising results and clinical progress. The review concludes with insights into patents, future directions, and the potential impact of PROTACs in addressing dysregulated protein expression across various diseases. Overall, it provides a concise yet comprehensive overview for researchers, clinicians, and industry professionals involved in developing targeted therapies.Graphical AbstractOverview of various PROTACs and their application in cancer therapy. PROTACs, consisting of an E3 ligase recruiter and a ligand for the protein of interest (POI), induce targeted cancer cell degradation. The figure highlights different types of PROTACs, including CLIPTACs, PhotoPROTACs, and Ab-PROTAC Conjugates, as well as the role of nanotechnology in enhancing their therapeutic effectiveness.