Evidence map›Paper›PMID 42775229›Full record

ReviewFrontiers in immunology2026

Targeted protein degradation dismantles undruggable targets to reverse immune evasion and therapy resistance in cancer.

Furong Zhang, Qianheng Wang, Mingxuan Li, Tingting Wang, Ping Lei, Tao Huang, Zhenghao Wu

Abstract readReview
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Furong Zhang *Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Qianheng Wang *Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Mingxuan LiDepartment of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Tingting WangDepartment of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Ping LeiDepartment of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Tao HuangDepartment of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Zhenghao WuDepartment of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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.

Indexed as

Drug Resistance, NeoplasmNeoplasmsTumor EscapeAnimalsHumansImmune EvasionImmunotherapyMolecular Targeted TherapyProteasome Endopeptidase ComplexProteolysisProteolysis Targeting ChimeraTumor MicroenvironmentProteasome Endopeptidase ComplexProteolysis Targeting Chimeracancerimmune evasiontargeted protein degradationtherapy resistanceundruggable targets

Identifiers

PMID42775229
PMCPMC13595565

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.