WITHDRAWN: Targeted protein degradation: A promising approach for cancer treatment

Abstract

Targeted protein degradation (TPD) is a promising approach that has the ability to address disease-causing proteins. Compared to traditional inhibition, proteolysis targeting chimera (PROTAC) technology offers various benefits, including the potential to target mutant and overexpressed proteins along with characteristics to target undruggable proteomes. A significant obstacle to the ongoing effective treatment of malignancies is cancer drug resistance, which is developed frequently by mutated or overexpressed protein targets and causes current remedies to continuously lose their effectiveness. The effective use of PROTACs to degrade targets that have undergone mutations and conferred resistance to first-line cancer therapies has attracted much research attention. To find novel/effective treatments, we analyzed the advancements in PROTACs aimed at cancer resistance and targets. This review provides a description of how PROTAC-based anticancer drugs are currently being developed and how to counter resistance if developed to PROTAC technology. Moreover, modern technologies related to protein degradation, including autophagy-targeting chimeras (AUTAC), lysosome-targeting chimeras (LYTAC), antibody-based PROTAC (AbTAC), Glue-body chimeras (GlueTAC), transcription-factor-targeting chimeras (TRAFTAC), RNA-PROTAC, aptamer-PROTAC, Photo-PROTAC, folate-PROTAC, and in-cell click-formed proteolysis targeting chimeras (CLIPTACs), have been discussed along with their mechanisms of action.