Target protein degradation by protacs: A budding cancer treatment strategy

• Published in: Pharmacology & therapeutics (Oxford) Vol. 250; p. 108525
• Main Authors: Choudhary, Diksha, Kaur, Amritpal, Singh, Pargat, Chaudhary, Gaurav, Kaur, Rajwinder, Bayan, Mohammad F., Chandrasekaran, Balakumar, Marji, Saeed M., Ayman, Reema
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01-10-2023
• Subjects: Cancer; E3 ligases; PROTACs; Protein degradation; Ubiquitination; Protein degradation; PFKFB3; FLT3; NEDD8; EGFR; FOXO1; SC; Ubiquitination; NAMPT; ERK1, 2; mTOR; TGF-β; UPS; c-MET; ISG; CRISPR; UV; E3 ligases; RNAi; VEGER 2; PROTACs; MAPK; FGFR; IV; Ub; JAK; DNA; AMPK; GPCR; GAPDH; PDGEFR; TDM-2; Cancer
• ISSN: 0163-7258; 1879-016X
• DOI: 10.1016/j.pharmthera.2023.108525

Cancer is one of the most common causes of death. So, its lethal effect increases with time. Near about hundreds of cancers are known in humans. Cancer treatment is done to cure or prolonged remission, and shrinkage of the tumor. Cytotoxic agents, biological agents/targeted drugs, hormonal drugs, surgery, radiotherapy/proton therapy, chemotherapy, immunotherapy, and gene therapy are currently used in the treatment of cancer but their cost is high and cause various side effects. Seeing this, some new targeted strategies such as PROTACs are the need of the time. Proteolysis targeting chimera (PROTAC) has become one of the most discussed topics regarding cancer treatment. Few of the PROTAC molecules are in the trial phases. PROTACs have many advantages over other strategies such as modularity, compatibility, sub-stoichiometric activity, acting on undruggable targets, molecular design, and acts on intracellular targets, selectivity and specificity can be recruited for any cancer, versatility, and others. PROTACs are having some unclear questions on their pharmacokinetics, heavy-molecular weight, etc. PROTACs are anticipated to bring about a conversion in current healthcare and will emerge as booming treatments. In this review article we summarize PROTACs, their mechanism of action, uses, advantages, disadvantages, challenges, and future aspects for the successful development of potent PROTACs as a drug strategy.