Yu Chen, Qingfan Yang, Jinrun Xu, Liyao Tang, Yan Zhang, Fukuan Du, Yueshui Zhao, Xu Wu, Mingxing Li, Jing Shen, Ruilin Ding, Hongying Cao, Wanping Li, Xiaobing Li, Meijuan Chen, Zhigui Wu, Chi Hin Cho, Yu Du, Qinglian Wen, Zhangang Xiao
Author Information
Yu Chen: Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou 646000, China.
Qingfan Yang: Department of Oncology, The Affiliated Hospital of Southwest Medical University, Southwest Medical University, Luzhou 646000, China.
Jinrun Xu: Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou 646000, China.
Liyao Tang: Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou 646000, China.
Yan Zhang: Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou 646000, China.
Fukuan Du: Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou 646000, China.
Yueshui Zhao: Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou 646000, China.
Xu Wu: Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou 646000, China.
Mingxing Li: Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou 646000, China.
Jing Shen: Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou 646000, China.
Ruilin Ding: Institute of Drug Clinical Trial/GCP Center, The Affiliated Hospital of Southwest Medical University, Southwest Medical University, Luzhou 646000, China.
Hongying Cao: Department of Emergency, The Affiliated Hospital of Southwest Medical University, Southwest Medical University, Luzhou 646000, China.
Wanping Li: Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou 646000, China.
Xiaobing Li: Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou 646000, China.
Meijuan Chen: Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou 646000, China.
Zhigui Wu: Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou 646000, China.
Chi Hin Cho: Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou 646000, China.
Yu Du: Medical Cosmetology Center, Affiliated Hospital of Traditional Chinese Medicine, Southwest Medical University, Luzhou 646000, China.
Qinglian Wen: Department of Oncology, The Affiliated Hospital of Southwest Medical University, Southwest Medical University, Luzhou 646000, China.
Zhangang Xiao: Department of Oncology, The Affiliated Hospital of Southwest Medical University, Southwest Medical University, Luzhou 646000, China.
Proteolysis targeting chimera (PROTAC) presents a powerful strategy for targeted protein degradation (TPD). The heterobifunctional PROTAC molecule consists of an E3 ligase ligand covalently linked to a protein of interest (POI) via a linker. PROTAC can induce ubiquitinated proteasomal degradation of proteins by hijacking the ubiquitin-proteasome degradation system (UPS). This technique has the advantages of broad targeting profile, good cell permeability, tissue specificity, high selectivity, oral bioavailability, and controllability. To date, a growing number of PROTACs targeting gastrointestinal cancers have been successfully developed, and, in many cases, their POIs have been validated as clinical drug targets. To the best of our knowledge, 15 PROTACs against various targets are currently tested in clinical trials, and many more are likely to be added in the near future. Therefore, this paper details the mechanism, research progress, and application in clinical trials of PROTACs, and summarizes the research achievements related to PROTACs in gastrointestinal cancers. Finally, we discuss the advantages and potential challenges of PROTAC for cancer treatment.
