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The discovery of proteolysis-targeting chimeras (PROTACs)6 is among the most exciting and promising avenues in cancer therapy. 14 These fascinating compounds signify a paradigm shift from traditional approaches to medication development, offering a new idea that leverages the complexities of biological mechanisms to accomplish highly focused degradation of particular proteins implicated in pathological processes.16 This novel strategy has the potential to address a number of drawbacks with conventional therapy techniques, such as the development of drug resistance and unexpected adverse effects resulting from interactions that are not intended. 14 The fundamental attraction of PROTACs is their distinct mode of action, which is based on controlling the cell's own machinery for protein degradation.11 This orchestrated degradation translates to a substantial reduction in the levels of disease-driving proteins, often leading to the disruption of critical pathways involved in cancer growth and progression.9 The in-depth principles underlying PROTAC technology are thoroughly explored in this review study, which also provides insight into the complex chemical mechanisms that enable these chimeric molecules to specifically degrade certain proteins while leaving others intact. Showcasing the potential of PROTACs as a revolutionary force in targeted cancer therapy, and focusing on its application in prostate and breast cancer especially, the article draws from a comprehensive compilation of preclinical and clinical studies, advancements, and breakthroughs in the field. 10 The methods used to create and refine PROTACs for various cancer types will be examined throughout the review, along with the subtleties of the ligand and linker choices that are crucial to their effectiveness and selectivity.6 The difficulties and possibilities of transferring this ground-breaking technology from the lab to clinical practice will also be thoroughly examined, with an emphasis on issues like bioavailability, administration strategies, and potential resistance mechanisms.9 Through the integration of perspectives from various studies, the objective is to present a thorough but succinct review of the state of ongoing PROTAC research, emphasizing both, noteworthy advancements and the important issues that still need to be resolved. In the end, our investigation into PROTACs aims to shed light on how they can change the face of cancer therapy by providing a preview of a day when targeted protein degradation of disease-causing proteins would lead the way in novel therapeutic approaches.9
Kumar et al. (Wed,) studied this question.