ReviewFrontiers in immunology2026
Targeted protein degradation dismantles undruggable targets to reverse immune evasion and therapy resistance in cancer.
Review in Frontiers in immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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7 authors.
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Abstract
Targeted protein degradation (TPD) harnesses endogenous proteolytic machineries-the ubiquitin-proteasome system and lysosomal pathways-to selectively eliminate disease-causing proteins that are refractory to conventional inhibition. In cancer immunotherapy, TPD dismantles critical immunosuppressive nodes across extracellular, membrane and intracellular compartments, reprogramming the tumor microenvironment from an immunologically 'cold' to a 'hot' state. This Review examines the molecular engineering principles of bifunctional degraders and summarizes clinical progress demonstrating synergy with immune checkpoint blockade and adoptive cell therapy. We discuss how catalytic protein elimination overcomes primary immune evasion and adaptive resistance driven by compensatory signaling, target mutation and metabolic rewiring. Finally, we outline translational roadblocks in cell-specific delivery, therapeutic window optimization and on-target/off-tissue toxicity mitigation, and propose engineering strategies to advance the clinical implementation of targeted protein degradation in immuno-oncology.
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