Small Molecules Targeting the PD-1/PD-L1 Axis for Cancer Immunotherapy
Date
Authors
Yin, Jia-Yi
Liu, Hui-Min
Li, Shao-long
Ji, Xin-Qian
Wang, Jun-Jie
Fu, Meng-Jie
Liu, Cong-Jun
Wang, Ning
Lu, Guo-Liang
Li, Yan
Supervisor
Item type
Journal Article
Degree name
Journal Title
Journal ISSN
Volume Title
Publisher
Ivyspring International Publisher
Abstract
PD-1/PD-L1 pathway, a key immune checkpoint, triggers T-cell exhaustion via binding and aiding tumor immune evasion. Although several anti-PD-1/PD-L1 monoclonal antibodies (mAbs) have been granted food and drug administration (FDA) approval, their high cost, poor oral bioavailability, and potential immunogenicity have led to a shift in research toward small molecules. This review summarizes the structure and function of PD-1/PD-L1 and, based on the PD-1/PD-L1 signaling process, focuses on three major classes of related compounds: small molecule inhibitors inducing PD-L1 dimerization or blocking PD-1/PD-L1 binding; PD-L1 degraders (e.g., Proteolysis-targeting chimeras (PROTACs) and Lysosome-targeting chimeras (LYTACs)) via the ubiquitin-proteasome or lysosomal pathway, overcoming membrane protein targeting; and dual-target inhibitors that enhance therapeutic efficacy by exerting synergistic effects. While small molecule drugs have advantages over monoclonal antibodies, including oral administration and reduced immunogenicity, they face drug resistance and toxicity challenges. This review aims to provide insights into the discovery of safe and effective antitumor immunotherapeutic agents.Description
Keywords
32 Biomedical and Clinical Sciences, 3211 Oncology and Carcinogenesis, 1112 Oncology and Carcinogenesis, 3211 Oncology and carcinogenesis
Source
Theranostics, ISSN: 1838-7640 (Print), Ivyspring International Publisher, 16(11), 6051-6080. doi: 10.7150/thno.130935
Publisher's version
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