Proteolysis-targeting chimeras (PROTACs) as novel biotechnology for cancer therapy

Chemotherapy has been widely used as the major therapy for the treatment of cancers by targeting disease-related proteins. The biological function of only a small part of these proteins with enzymatic activity and accessible binding sites can be inhibited by small molecular inhibitors or monoclonal antibodies. Chemotherapy is often blocked by resistance to chemotherapy drugs. Therefore, new biotechnology has been developed, which is based on PROTACs, proteolysis-targeting chimeric molecules for targeted protein degradation. PROTACs are bifunctional molecules designed to polyubiquitinate and degrade specific pathological proteins of interest by hijacking the activity of E3-ubiquitin ligases for POI polyubiquitination and subsequent degradation by the proteasome. This strategy utilizes the ubiquitin-proteasome system for the degradation of specific proteins in the cell. In many cases, including solid tumors and hematologic malignancies, inducing protein degradation as a therapeutic strategy offers a therapeutic benefit over classical enzyme inhibition connected with resistance to inhibitors.