New strategies for targeting PD-1/PD-L1: degraders, bifunctional molecules and covalent inhibitors

Programmed cell death protein-1 (PD-1) / programmed cell death ligand-1 (PD-L1) has been considered to be one of the most promising targets for tumor immunotherapy. At present, both monoclonal antibody drugs and small molecule inhibitors targeting PD-1/PD-L1 are facing bottlenecks. Numerous researchers have tried to explore different strategies to block the PD-L1/PD-L1 pathway, hoping to improve the effects of tumor immunotherapy. This review focuses on the degraders, bifunctional molecules and covalent inhibitors that target PD-L1, aiming to provide inspiring insights for the development of anti-PD-1/PD-L1 drugs.