{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T00:33:09Z","timestamp":1793147589626,"version":"4.5.0"},"reference-count":192,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Targeted protein degradation (TPD) harnesses endogenous proteolytic machineries\u2014the ubiquitin\u2013proteasome system and lysosomal pathways\u2014to 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 \u2018cold\u2019 to a \u2018hot\u2019 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.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1935909","type":"journal-article","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T13:47:28Z","timestamp":1788875248000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Targeted protein degradation dismantles undruggable targets to reverse immune evasion and therapy resistance in cancer"],"prefix":"10.3389","volume":"17","author":[{"given":"Furong","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, China"]},{"name":"Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianheng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, China"]},{"name":"Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingxuan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Lei","sequence":"additional","affiliation":[{"name":"Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenghao","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, China"]},{"name":"Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, China"]},{"name":"Guangdong Provincial Key Laboratory of Malignant Tumour Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for ribonucleic acid (RNA) Medicine, Breast Tumour Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.141230798","article-title":"Protacs: chimeric molecules that target proteins to the Skp1\u2013cullin\u2013F box complex for ubiquitination and degradation","volume":"98","author":"Sakamoto","year":"2001","journal-title":"Proc Natl Acad Sci USA"},{"key":"B2","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1038\/s41573-021-00371-6","article-title":"PROTAC targeted protein degraders: the past is prologue","volume":"21","author":"B\u00e9k\u00e9s","year":"2022","journal-title":"Nat Rev Drug Discov"},{"key":"B3","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1038\/s41568-025-00817-8","article-title":"Targeted protein degradation for cancer therapy","volume":"25","author":"Hinterndorfer","year":"2025","journal-title":"Nat Rev Cancer"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-021-00245-x","article-title":"The PROTACtable genome","volume":"20","author":"Schneider","year":"2021","journal-title":"Nat Rev Drug Discov"},{"key":"B5","doi-asserted-by":"publisher","first-page":"LBA1000","DOI":"10.1200\/JCO.2025.43.17_suppl.LBA1000","article-title":"Vepdegestrant, a PROTAC estrogen receptor (ER) degrader, vs fulvestrant in ER-positive\/human epidermal growth factor receptor 2 (HER2)\u2013negative advanced breast cancer: results of the global, randomized, phase 3 VERITAC-2 study","volume":"43","author":"Hamilton","year":"2025","journal-title":"J Clin Oncol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"4433","DOI":"10.1182\/blood-2024-210301","article-title":"Safety, pharmacokinetics, pharmacodynamics and clinical activity of KT-333, a targeted protein degrader of STAT3, in patients with relapsed or refractory lymphomas, leukemia, and solid tumors","volume":"144","author":"Feldman","year":"2024","journal-title":"Blood"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2545-9","article-title":"Lysosome-targeting chimaeras for degradation of extracellular proteins","volume":"584","author":"Banik","year":"2020","journal-title":"Nature"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.0c10008","article-title":"Development of antibody-based PROTACs for the degradation of the cell-surface immune checkpoint protein PD-L1","volume":"143","author":"Cotton","year":"2021","journal-title":"J Am Chem Soc"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/d41573-022-00055-9","article-title":"Targeted protein degraders: a call for collective action to advance safety assessment","volume":"21","author":"Jones","year":"2022","journal-title":"Nat Rev Drug Discov"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1039\/D5CC05651A","article-title":"Programmable PROTAC delivery for precise and spatiotemporal protein degradation","volume":"62","author":"Sheng","year":"2026","journal-title":"Chem Commun"},{"key":"B11","doi-asserted-by":"publisher","first-page":"6784","DOI":"10.1016\/j.cell.2024.10.025","article-title":"SnapShot: targeted protein degradation","volume":"187","author":"Ding","year":"2024","journal-title":"Cell"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2024.104178","article-title":"Targeted protein degradation: current molecular targets, localization, and strategies","volume":"29","author":"Pliatsika","year":"2024","journal-title":"Drug Discov Today"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1038\/nrc.2017.36","article-title":"Drugging the \u201cundruggable\u201d cancer targets","volume":"17","author":"Dang","year":"2017","journal-title":"Nat Rev Cancer"},{"key":"B14","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1038\/s41392-023-01522-4","article-title":"Immune checkpoint therapy for solid tumours: clinical dilemmas and future trends","volume":"8","author":"Sun","year":"2023","journal-title":"Signal Transduction Targeted Ther"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2026.153330","article-title":"Clinical advances in CD47-SIRP\u03b1 axis-targeted cancer immunotherapy: mechanisms, strategies, challenges, and future perspectives","volume":"802","author":"Li","year":"2026","journal-title":"Biochem Biophys Res Commun"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-023-00833-z","article-title":"Extracellular targeted protein degradation: an emerging modality for drug discovery","volume":"23","author":"Wells","year":"2024","journal-title":"Nat Rev Drug Discov"},{"key":"B17","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1038\/s41392-022-00966-4","article-title":"Targeted protein degradation: mechanisms, strategies and application","volume":"7","author":"Zhao","year":"2022","journal-title":"Signal Transduct Target Ther"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1002\/pro.70051","article-title":"Engineering IGF2 for lysosome\u2010targeting chimeras development to target drug\u2010resistant membrane proteins in tumor therapy","volume":"34","author":"Pan","year":"2025","journal-title":"Protein Sci"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-07947-3","article-title":"Transferrin receptor targeting chimeras for membrane protein degradation","volume":"638","author":"Zhang","year":"2025","journal-title":"Nature"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.2c08367","article-title":"Bifunctional compounds as molecular degraders for integrin-facilitated targeted protein degradation","volume":"144","author":"Zheng","year":"2022","journal-title":"J Am Chem Soc"},{"key":"B21","doi-asserted-by":"publisher","first-page":"8695","DOI":"10.1038\/s41467-024-52685-9","article-title":"Development of folate receptor targeting chimeras for cancer selective degradation of extracellular proteins","volume":"15","author":"Zhou","year":"2024","journal-title":"Nat Commun"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202300288","article-title":"Nano\u2010LYTACs for degradation of membrane proteins and inhibition of CD24\/siglec\u201010 signaling pathway","volume":"10","author":"Wang","year":"2023","journal-title":"Adv Sci (Weinh)"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.5c13695","article-title":"Development of dual-receptor lysosome-targeting chimeras for protein degradation","volume":"147","author":"Wang","year":"2025","journal-title":"J Am Chem Soc"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202218106","article-title":"Aptamer-LYTACs for targeted degradation of extracellular and membrane proteins","volume":"62","author":"Wu","year":"2023","journal-title":"Angew Chem Int Ed"},{"key":"B25","doi-asserted-by":"publisher","first-page":"7575","DOI":"10.1038\/s41467-025-62776-w","article-title":"Targeted degradation of cell surface proteins through endocytosis triggered by cell-penetrating peptide-small molecule conjugates","volume":"16","author":"He","year":"2025","journal-title":"Nat Commun"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-05235-6","article-title":"Antibody targeting of E3 ubiquitin ligases for receptor degradation","volume":"610","author":"Marei","year":"2022","journal-title":"Nature"},{"key":"B27","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1038\/s41587-023-01840-6","article-title":"Design of a mucin-selective protease for targeted degradation of cancer-associated mucins","volume":"42","author":"Pedram","year":"2024","journal-title":"Nat Biotechnol"},{"key":"B28","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1038\/nrd.2016.199","article-title":"Aptamers as targeted therapeutics: current potential and challenges","volume":"16","author":"Zhou","year":"2017","journal-title":"Nat Rev Drug Discov"},{"key":"B29","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1038\/s41392-024-02004-x","article-title":"Targeted protein degradation: advances in drug discovery and clinical practice","volume":"9","author":"Zhong","year":"2024","journal-title":"Signal Transduction Targeted Ther"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellin.2025.100295","article-title":"Hydrophobic tagging: a promising paradigm for targeted protein degradation","volume":"5","author":"Xin","year":"2026","journal-title":"Cell Insight"},{"key":"B31","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1016\/j.molcel.2019.09.009","article-title":"AUTACs: cargo-specific degraders using selective autophagy","volume":"76","author":"Takahashi","year":"2019","journal-title":"Mol Cell"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1722-1","article-title":"Allele-selective lowering of mutant HTT protein by HTT-LC3 linker compounds","volume":"575","author":"Li","year":"2019","journal-title":"Nature"},{"key":"B33","doi-asserted-by":"publisher","first-page":"904","DOI":"10.1038\/s41467-022-28520-4","article-title":"The AUTOTAC chemical biology platform for targeted protein degradation via the autophagy-lysosome system","volume":"13","author":"Ji","year":"2022","journal-title":"Nat Commun"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.10.033","article-title":"A method for the acute and rapid degradation of endogenous proteins","volume":"171","author":"Clift","year":"2017","journal-title":"Cell"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1021\/acscentsci.6b00280","article-title":"Protein degradation by in-cell self-assembly of proteolysis targeting chimeras","volume":"2","author":"Lebraud","year":"2016","journal-title":"ACS Cent Sci"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1038\/s41589-022-00971-2","article-title":"Deubiquitinase-targeting chimeras for targeted protein stabilization","volume":"18","author":"Henning","year":"2022","journal-title":"Nat Chem Biol"},{"key":"B37","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1186\/s13045-020-00885-3","article-title":"Proteolysis-targeting chimera (PROTAC) for targeted protein degradation and cancer therapy","volume":"13","author":"Li","year":"2020","journal-title":"J Hematol Oncol"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2025.117297","article-title":"Molecular glues and PROTACs in targeted protein degradation: mechanisms, advances, and therapeutic potential","volume":"242","author":"Eladl","year":"2025","journal-title":"Biochem Pharmacol"},{"key":"B39","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.cell.2020.12.020","article-title":"The rise of molecular glues","volume":"184","author":"Schreiber","year":"2021","journal-title":"Cell"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2026.02.020","article-title":"Molecular glue degraders: rational design, specificity engineering, and advanced delivery","volume":"16","author":"Ma","year":"2026","journal-title":"Acta Pharm Sin B"},{"key":"B41","doi-asserted-by":"publisher","first-page":"4460","DOI":"10.1038\/s41467-026-70663-1","article-title":"A dihydrouracil CRBN ligand mitigates IMiD associated safety liabilities in heterobifunctional targeted protein degrader","volume":"17","author":"Rodrigo-Brenni","year":"2026","journal-title":"Nat Commun"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.0c00793","article-title":"Understanding the metabolism of proteolysis targeting chimeras (PROTACs): the next step toward pharmaceutical applications","volume":"63","author":"Goracci","year":"2020","journal-title":"J Med Chem"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2021.03.042","article-title":"Antibody-drug conjugates: recent advances in linker chemistry","volume":"11","author":"Su","year":"2021","journal-title":"Acta Pharm Sin B"},{"key":"B44","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1007\/s13238-016-0323-0","article-title":"Antibody-drug conjugates: recent advances in conjugation and linker chemistries","volume":"9","author":"Tsuchikama","year":"2018","journal-title":"Protein Cell"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1039\/d5cc03325j","article-title":"Click chemistry enables rapid development of potent sEH PROTACs using a direct-to-biology approach","volume":"61","author":"Sch\u00f6nfeld","year":"2025","journal-title":"Chem Commun"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2925-1","article-title":"Small-molecule-induced polymerization triggers degradation of BCL6","volume":"588","author":"S\u0142abicki","year":"2020","journal-title":"Nature"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2022.03.004","article-title":"Intercellular signaling by ectodomain shedding at the synapse","volume":"45","author":"Mart\u00edn-de-Saavedra","year":"2022","journal-title":"Trends Neurosci"},{"key":"B48","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/978-1-4939-3804-9_1","article-title":"ER to golgi-dependent protein secretion: the conventional pathway","volume-title":"Unconventional Protein Secretion: Methods and Protocols","author":"Viotti","year":"2016"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-022-01456-2","article-title":"Modular cytokine receptor-targeting chimeras for targeted degradation of cell surface and extracellular proteins","volume":"41","author":"Pance","year":"2023","journal-title":"Nat Biotechnol"},{"key":"B50","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1038\/s41589-018-0161-x","article-title":"HIP1R targets PD-L1 to lysosomal degradation to alter T cell\u2013mediated cytotoxicity","volume":"15","author":"Wang","year":"2019","journal-title":"Nat Chem Biol"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2020.112377","article-title":"Discovery of novel resorcinol diphenyl ether-based PROTAC-like molecules as dual inhibitors and degraders of PD-L1","volume":"199","author":"Cheng","year":"2020","journal-title":"Eur J Med Chem"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-023-01612-z","article-title":"Nutrition impact on ILC3 maintenance and function centers on a cell-intrinsic CD71\u2013iron axis","volume":"24","author":"Xiong","year":"2023","journal-title":"Nat Immunol"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1456-0","article-title":"CD24 signalling through macrophage siglec-10 is a target for cancer immunotherapy","volume":"572","author":"Barkal","year":"2019","journal-title":"Nature"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2022-004589","article-title":"CD47\/SIRP\u03b1 axis: Bridging innate and adaptive immunity","volume":"10","author":"van Duijn","year":"2022","journal-title":"J Immunother Cancer"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2021.108024","article-title":"Macrophage migration inhibitory factor (MIF): A multifaceted cytokine regulated by genetic and physiological strategies","volume":"233","author":"Sumaiya","year":"2022","journal-title":"Pharmacol Ther"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2021-003180","article-title":"Recombinant mycobacterium smegmatis delivering a fusion protein of human macrophage migration inhibitory factor (MIF) and IL-7 exerts an anticancer effect by inducing an immune response against MIF in a tumor-bearing mouse model","volume":"9","author":"Jeong","year":"2021","journal-title":"J Immunother Cancer"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202101864","article-title":"Proteolysis targeting chimera (PROTAC) for macrophage migration inhibitory factor (MIF) has anti\u2010proliferative activity in lung cancer cells","volume":"60","author":"Xiao","year":"2021","journal-title":"Angew Chem Int Ed Engl"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202500311","article-title":"A self\u2010assembling LYTAC mediates CTGF degradation and remodels inflammatory tumor microenvironment for triple\u2010negative breast cancer therapy","volume":"12","author":"Lin","year":"2025","journal-title":"Adv Sci (Weinh)"},{"key":"B59","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1186\/s40164-025-00692-x","article-title":"Targeted degradation of sICOSL reverses cytotoxic T cells dysfunction","volume":"14","author":"Wu","year":"2025","journal-title":"Exp Hematol Oncol"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2024-011445","article-title":"Tumor-secreted galectin-3 suppresses antitumor response by inducing IL-10+ B cells","volume":"13","author":"Zheng","year":"2025","journal-title":"J Immunother Cancer"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202509921","article-title":"Targeted degradation of sGRP78 alleviates the immunosuppressive tumor microenvironment","volume":"12","author":"Wu","year":"2025","journal-title":"Adv Sci"},{"key":"B62","doi-asserted-by":"publisher","first-page":"587","DOI":"10.1038\/s41419-022-05048-5","article-title":"sGRP78 enhances selective autophagy of monomeric TLR4 to regulate myeloid cell death","volume":"13","author":"Wu","year":"2022","journal-title":"Cell Death Dis"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-023-01150-6","article-title":"Soluble receptors in cancer: Mechanisms, clinical significance, and therapeutic strategies","volume":"56","author":"Park","year":"2024","journal-title":"Exp Mol Med"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1039\/D2CS00141A","article-title":"Degrader-antibody conjugates","volume":"51","author":"Dragovich","year":"2022","journal-title":"Chem Soc Rev"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1021\/acschembio.0c00285","article-title":"Antibody-PROTAC conjugates enable HER2-dependent targeted protein degradation of BRD4","volume":"15","author":"Maneiro","year":"2020","journal-title":"ACS Chem Biol"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2026.102948","article-title":"An antibody-PROTAC conjugate targets BRD4\/c-myc\/PD-L1 to enhance immunotherapy efficacy in triple-negative breast cancer","volume":"7","author":"Gu","year":"2026","journal-title":"Cell Rep Med"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2019.126907","article-title":"Antibody-mediated delivery of chimeric protein degraders which target estrogen receptor alpha (ER\u03b1)","volume":"30","author":"Dragovich","year":"2020","journal-title":"Bioorg Med Chem Lett"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-025-01765-4","article-title":"Recent advances in targeting protein degradation for tumor immunotherapy","volume":"19","author":"Li","year":"2025","journal-title":"J Hematol Oncol"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1021\/acschembio.2c00185","article-title":"Roadmap for optimizing and broadening antibody-based PROTACs for degradation of cell surface proteins","volume":"17","author":"Gramespacher","year":"2022","journal-title":"ACS Chem Biol"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.adr7057","article-title":"Inducible protein degradation reveals inflammation-dependent function of the treg cell lineage-defining transcription factor Foxp3","volume":"10","author":"J\u00e4ger","year":"2025","journal-title":"Sci Immunol"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2017.75","article-title":"The regulation of immune tolerance by FOXP3","volume":"17","author":"Lu","year":"2017","journal-title":"Nat Rev Immunol"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1402997","article-title":"Inhibition of FOXP3\/NFAT interaction enhances T cell function after TCR stimulation","volume":"195","author":"Lozano","year":"2015","journal-title":"J Immunol"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1001114","article-title":"A peptide inhibitor of FOXP3 impairs regulatory T cell activity and improves vaccine efficacy in mice","volume":"185","author":"Casares","year":"2010","journal-title":"J Immunol"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0156643","article-title":"Epirubicin, identified using a novel luciferase reporter assay for Foxp3 inhibitors, inhibits regulatory T cell activity","volume":"11","author":"Kashima","year":"2016","journal-title":"PloS One"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2209044119","article-title":"Inhibition of FOXP3 by stapled alpha-helical peptides dampens regulatory T cell function","volume":"119","author":"Hawley","year":"2022","journal-title":"Proc Natl Acad Sci USA"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2023.114871","article-title":"Stimulation of antitumor immunity by FoxP3-targeting PROTAC","volume":"163","author":"Wang","year":"2023","journal-title":"Biomedicine Pharmacotherapy"},{"key":"B77","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1038\/s41586-025-09000-3","article-title":"STAT5 and STAT3 balance shapes dendritic cell function and tumour immunity","volume":"643","author":"Zhou","year":"2025","journal-title":"Nature"},{"key":"B78","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1038\/s41392-025-02363-z","article-title":"Neutrophil-specific targeting of STAT3 impairs tumor progression via the expansion of cytotoxic CD8+ T cells","volume":"10","author":"Ozel","year":"2025","journal-title":"Sig Transduct Target Ther"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbcan.2025.189461","article-title":"STAT3 axis in cancer and cancer stem cells: From oncogenesis to targeted therapies","volume":"1880","author":"Godugu","year":"2025","journal-title":"Biochim Biophys Acta (BBA) - Rev Cancer"},{"key":"B80","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1016\/j.pharmthera.2018.06.006","article-title":"Two decades of research in discovery of anticancer drugs targeting STAT3, how close are we","volume":"191","author":"Beebe","year":"2018","journal-title":"Pharmacol Ther"},{"key":"B81","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1016\/j.ccell.2019.10.002","article-title":"A potent and selective small-molecule degrader of STAT3 achieves complete tumor regression in vivo","volume":"36","author":"Bai","year":"2019","journal-title":"Cancer Cell"},{"key":"B82","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1186\/s13046-024-02949-5","article-title":"Unraveling the complexity of STAT3 in cancer: Molecular understanding and drug discovery","volume":"43","author":"Hu","year":"2024","journal-title":"J Exp Clin Cancer Research: CR"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.11.031","article-title":"Proteolysis-targeting chimeras as therapeutics and tools for biological discovery","volume":"181","author":"Burslem","year":"2020","journal-title":"Cell"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1039\/D2CS00339B","article-title":"The importance of cellular degradation kinetics for understanding mechanisms in targeted protein degradation","volume":"51","author":"Riching","year":"2022","journal-title":"Chem Soc Rev"},{"key":"B85","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1038\/s42003-020-0868-6","article-title":"Extended pharmacodynamic responses observed upon PROTAC-mediated degradation of RIPK2","volume":"3","author":"Mares","year":"2020","journal-title":"Commun Biol"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-023-02635-7","article-title":"IRAK4 degrader in hidradenitis suppurativa and atopic dermatitis: A phase 1 trial","volume":"29","author":"Ackerman","year":"2023","journal-title":"Nat Med"},{"key":"B87","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1016\/j.xphs.2023.10.027","article-title":"Pharmacodynamic models of indirect effects and irreversible inactivation with turnover: applicability to mechanism-based modeling of gene silencing and targeted protein degradation","volume":"113","author":"Wang","year":"2024","journal-title":"J Pharm Sci"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-023-01718-4","article-title":"IKAROS and AIOLOS directly regulate AP-1 transcriptional complexes and are essential for NK cell development","volume":"25","author":"Goh","year":"2024","journal-title":"Nat Immunol"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2024.101571","article-title":"Pharmacodynamic changes in tumor and immune cells drive iberdomide\u2019s clinical mechanisms of activity in relapsed and refractory multiple myeloma","volume":"5","author":"Amatangelo","year":"2024","journal-title":"Cell Rep Med"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3026(22)00290-3","article-title":"Iberdomide plus dexamethasone in heavily pretreated late-line relapsed or refractory multiple myeloma (CC-220-MM-001): A multicentre, multicohort, open-label, phase 1\/2 trial","volume":"9","author":"Lonial","year":"2022","journal-title":"Lancet Haematol"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2024.09.008","article-title":"Emerging interleukin-1 receptor-associated kinase 4 (IRAK4) inhibitors or degraders as therapeutic agents for autoimmune diseases and cancer","volume":"14","author":"Feng","year":"2024","journal-title":"Acta Pharm Sin B"},{"key":"B92","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.3c01823","article-title":"Discovery of KT-413, a targeted protein degrader of IRAK4 and IMiD substrates targeting MYD88 mutant diffuse large B-cell lymphoma","volume":"67","author":"Weiss","year":"2024","journal-title":"J Med Chem"},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.adh1306","article-title":"BCL6 promotes a stem-like CD8+ T cell program in cancer via antagonizing BLIMP1","volume":"8","author":"Sun","year":"2023","journal-title":"Sci Immunol"},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.5c03123","article-title":"Discovery of BMS-986458, a potent and selective B-cell lymphoma 6 protein ligand-directed degrader, for the treatment of B-cell non-hodgkin lymphoma","volume":"69","author":"Mortensen","year":"2026","journal-title":"J Med Chem"},{"key":"B95","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-04-347849","article-title":"Bcl-xL-inhibitory BH3 mimetics can induce a transient thrombocytopathy that undermines the hemostatic function of platelets","volume":"118","author":"Schoenwaelder","year":"2011","journal-title":"Blood"},{"key":"B96","doi-asserted-by":"publisher","first-page":"1281","DOI":"10.1038\/s41467-021-21573-x","article-title":"Proteolysis-targeting chimera against BCL-XL destroys tumor-infiltrating regulatory T cells","volume":"12","author":"Kolb","year":"2021","journal-title":"Nat Commun"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.1021\/acscentsci.5c00812","article-title":"Targeted NAT10 degradation by PROTAC NP1192 suppresses hypoxia-adaptive glycolysis and reinvigorates CD8+ effector T-cell function for synergistic cancer immunotherapy","volume":"11","author":"Ao","year":"2025","journal-title":"ACS Cent Sci"},{"key":"B98","doi-asserted-by":"publisher","first-page":"10683","DOI":"10.1038\/s41467-024-55006-2","article-title":"Development of a RIPK1 degrader to enhance antitumor immunity","volume":"15","author":"Yu","year":"2024","journal-title":"Nat Commun"},{"key":"B99","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-23-3465","article-title":"Oral estrogen receptor PROTAC vepdegestrant (ARV-471) is highly efficacious as monotherapy and in combination with CDK4\/6 or PI3K\/mTOR pathway inhibitors in preclinical ER+ breast cancer models","volume":"30","author":"Gough","year":"2024","journal-title":"Clin Cancer Res"},{"key":"B100","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(24)00387-5","article-title":"Camizestrant, a next-generation oral SERD, versus fulvestrant in post-menopausal women with oestrogen receptor-positive, HER2-negative advanced breast cancer (SERENA-2): A multi-dose, open-label, randomised, phase 2 trial","volume":"25","author":"Oliveira","year":"2024","journal-title":"Lancet Oncol"},{"key":"B101","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2502929","article-title":"First-line camizestrant for emerging ESR1-mutated advanced breast cancer","volume":"393","author":"Bidard","year":"2025","journal-title":"N Engl J Med"},{"key":"B102","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2024.217112","article-title":"PI3K PROTAC overcomes the lapatinib resistance in PIK3CA-mutant HER2 positive breast cancer","volume":"598","author":"Zhang","year":"2024","journal-title":"Cancer Lett"},{"key":"B103","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.2c01422","article-title":"Discovery of GDC-0077 (inavolisib), a highly selective inhibitor and degrader of mutant PI3K\u03b1","volume":"65","author":"Hanan","year":"2022","journal-title":"J Med Chem"},{"key":"B104","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1158\/1078-0432.CCR-25-1459","article-title":"PI3K\u03b1 inhibitor and degrader inavolisib can co-opt FGFR2 to enhance responses in patients with PIK3CA-mutated solid tumors and in preclinical models","volume":"32","author":"Juric","year":"2026","journal-title":"Clin Cancer Res"},{"key":"B105","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.4c03169","article-title":"Double swords in one: Novel selective PI3K\/110\u03b2 PROTAC degraders for the treatment of multidrug-resistant cancer by activating ERS and inhibiting P-gp","volume":"68","author":"Cen","year":"2025","journal-title":"J Med Chem"},{"key":"B106","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.5c02244","article-title":"Discovery of the first potent PI3K\/mTOR dual-targeting PROTAC degrader for efficient modulation of the PI3K\/AKT\/mTOR pathway","volume":"68","author":"Zhu","year":"2025","journal-title":"J Med Chem"},{"key":"B107","doi-asserted-by":"publisher","DOI":"10.1038\/s43018-024-00782-5","article-title":"Targeting a lineage-specific PI3K\u03b3\/AKT signaling module in acute myeloid leukemia using a heterobifunctional degrader molecule","volume":"5","author":"Kelly","year":"2024","journal-title":"Nat Cancer"},{"key":"B108","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.5c00679","article-title":"Discovery and optimization of potent PROTAC degraders of phosphoinositide 3-kinase with significant in vivo anticancer efficacy","volume":"68","author":"Peng","year":"2025","journal-title":"J Med Chem"},{"key":"B109","doi-asserted-by":"publisher","DOI":"10.1039\/D3SC04629J","article-title":"A high affinity pan-PI3K binding module supports selective targeted protein degradation of PI3K\u03b1","volume":"15","author":"Jauslin","year":"2024","journal-title":"Chem Sci"},{"key":"B110","doi-asserted-by":"publisher","DOI":"10.1021\/acscentsci.0c00411","article-title":"Targeted degradation of oncogenic KRASG12C by VHL-recruiting PROTACs","volume":"6","author":"Bond","year":"2020","journal-title":"ACS Cent Sci"},{"key":"B111","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.5c00428","article-title":"Discovery and characterization of RP03707: a highly potent and selective KRASG12D PROTAC","volume":"68","author":"Ji","year":"2025","journal-title":"J Med Chem"},{"key":"B112","doi-asserted-by":"publisher","first-page":"386","DOI":"10.1038\/s41392-021-00780-4","article-title":"KRAS mutation: from undruggable to druggable in cancer","volume":"6","author":"Huang","year":"2021","journal-title":"Signal Transduction Targeted Ther"},{"key":"B113","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1917239","article-title":"KRAS(G12C) inhibition with sotorasib in advanced solid tumors","volume":"383","author":"Hong","year":"2020","journal-title":"N Engl J Med"},{"key":"B114","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2023.115124","article-title":"Annual review of KRAS inhibitors in 2022","volume":"249","author":"Wang","year":"2023","journal-title":"Eur J Med Chem"},{"key":"B115","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1186\/s12943-025-02364-0","article-title":"Evolution of direct RAS inhibitors: from undruggable target to clinical breakthroughs","volume":"24","author":"Wang","year":"2025","journal-title":"Mol Cancer"},{"key":"B116","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.5c10354","article-title":"Identification of a highly cooperative PROTAC degrader targeting GTP-loaded KRAS(on) alleles","volume":"147","author":"Vetma","year":"2025","journal-title":"J Am Chem Soc"},{"key":"B117","doi-asserted-by":"publisher","DOI":"10.1039\/d5md00095e","article-title":"Razing the scaffolding: the elimination of non-catalytic functions of kinases through targeted protein degradation","volume":"16","author":"Pogash","year":"2025","journal-title":"RSC Med Chem"},{"key":"B118","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2026.118635","article-title":"Discovery of KRAS-G12D degraders via exploration of various E3 ligases","volume":"307","author":"Yim","year":"2026","journal-title":"Eur J Med Chem"},{"key":"B119","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2022-006581","article-title":"Androgen receptor blockade resistance with enzalutamide in prostate cancer results in immunosuppressive alterations in the tumor immune microenvironment","volume":"11","author":"Xu","year":"2023","journal-title":"J Immunother Cancer"},{"key":"B120","doi-asserted-by":"publisher","first-page":"6964","DOI":"10.1038\/s41467-025-62381-x","article-title":"AR+TREM2+ macrophage induced pathogenic immunosuppression promotes prostate cancer progression","volume":"16","author":"Wang","year":"2025","journal-title":"Nat Commun"},{"key":"B121","doi-asserted-by":"publisher","DOI":"10.1172\/JCI168649","article-title":"Androgen receptor splice variants drive castration-resistant prostate cancer metastasis by activating distinct transcriptional programs","volume":"134","author":"Han","year":"2024","journal-title":"J Clin Invest"},{"key":"B122","doi-asserted-by":"publisher","DOI":"10.1038\/d41573-025-00037-7","article-title":"Induced proximity pushes beyond protein degraders, as first RIPTAC moves into the clinic","volume":"24","author":"Mullard","year":"2025","journal-title":"Nat Rev Drug Discov"},{"key":"B123","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.5c01250","article-title":"RIPTACs for precision cancer therapy: A novel modality with the inspiration of HLD-0915 as the first candidate in clinical trials","volume":"68","author":"Ma","year":"2025","journal-title":"J Med Chem"},{"key":"B124","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-22-1131","article-title":"Targeted MDM2 degradation reveals a new vulnerability for p53 inactivated triple negative breast cancer","volume":"13","author":"Adams","year":"2023","journal-title":"Cancer Discov"},{"key":"B125","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2023.08.024","article-title":"Immunosuppressive CD10+ALPL+ neutrophils promote resistance to anti-PD-1 therapy in HCC by mediating irreversible exhaustion of T cells","volume":"79","author":"Meng","year":"2023","journal-title":"J Hepatol"},{"key":"B126","doi-asserted-by":"publisher","first-page":"1616","DOI":"10.1016\/j.chembiol.2022.10.007","article-title":"Addressing the enzyme-independent tumor-promoting function of NAMPT via PROTAC-mediated degradation","volume":"29","author":"Zhu","year":"2022","journal-title":"Cell Chem Biol"},{"key":"B127","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.4c00193","article-title":"Design of FK866-based degraders for blocking the nonenzymatic functions of nicotinamide phosphoribosyltransferase","volume":"67","author":"Lu","year":"2024","journal-title":"J Med Chem"},{"key":"B128","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.2c01243","article-title":"Making protein degradation visible: Discovery of theranostic PROTACs for detecting and degrading NAMPT","volume":"65","author":"Cheng","year":"2022","journal-title":"J Med Chem"},{"key":"B129","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.2c01990","article-title":"Discovery of highly potent nicotinamide phosphoribosyltransferase degraders for efficient treatment of ovarian cancer","volume":"66","author":"Bi","year":"2023","journal-title":"J Med Chem"},{"key":"B130","doi-asserted-by":"publisher","first-page":"1203","DOI":"10.1016\/j.chembiol.2024.05.007","article-title":"NAMPT-targeting PROTAC and nicotinic acid co-administration elicit safe and robust anti-tumor efficacy in NAPRT-deficient pan-cancers","volume":"31","author":"Zhu","year":"2024","journal-title":"Cell Chem Biol"},{"key":"B131","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1186\/s12943-022-01569-x","article-title":"Targeting TGF-\u03b2 signal transduction for fibrosis and cancer therapy","volume":"21","author":"Peng","year":"2022","journal-title":"Mol Cancer"},{"key":"B132","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aan5488","article-title":"Enhanced preclinical antitumor activity of M7824, a bifunctional fusion protein simultaneously targeting PD-L1 and TGF-\u03b2","volume":"10","author":"Lan","year":"2018","journal-title":"Sci Transl Med"},{"key":"B133","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.4c16628","article-title":"Multivalent aptamer assembly enhances tumor-specific degradation of transforming growth factor-beta to remodel the stromal and immunosuppressive cancer microenvironment","volume":"19","author":"Liu","year":"2025","journal-title":"ACS Nano"},{"key":"B134","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrp.2024.102339","article-title":"A heparanase-specific LYTAC degrader reinforces natural killer cell cytotoxicity within the tumor microenvironment","volume":"5","author":"Li","year":"2024","journal-title":"CR-PHYS-SC"},{"key":"B135","doi-asserted-by":"publisher","first-page":"8804","DOI":"10.1038\/s41467-025-63882-5","article-title":"Dual membrane receptor degradation via folate receptor targeting chimera","volume":"16","author":"Wang","year":"2025","journal-title":"Nat Commun"},{"key":"B136","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.3c01872","article-title":"Trends in neosubstrate degradation by cereblon-based molecular glues and the development of novel multiparameter optimization scores","volume":"67","author":"Szewczyk","year":"2024","journal-title":"J Med Chem"},{"key":"B137","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.4c01305","article-title":"Discovery of KT-474\u2014a potent, selective, and orally bioavailable IRAK4 degrader for the treatment of autoimmune diseases","volume":"67","author":"Zheng","year":"2024","journal-title":"J Med Chem"},{"key":"B138","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-025-09994-w","article-title":"Identification of an allosteric site on the E3 ligase adapter cereblon","volume":"651","author":"Dippon","year":"2026","journal-title":"Nature"},{"key":"B139","doi-asserted-by":"publisher","DOI":"10.1038\/s41589-018-0055-y","article-title":"Plasticity in binding confers selectivity in ligand-induced protein degradation","volume":"14","author":"Nowak","year":"2018","journal-title":"Nat Chem Biol"},{"key":"B140","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1146\/annurev-biochem-032620-104421","article-title":"Driving E3 ligase substrate specificity for targeted protein degradation: lessons from nature and the laboratory","volume":"91","author":"Cowan","year":"2022","journal-title":"Annu Rev Biochem"},{"key":"B141","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbpa.2024.102552","article-title":"Advances in acid-degradable and enzyme-cleavable linkers for drug delivery","volume":"84","author":"Zhao","year":"2025","journal-title":"Curr Opin Chem Biol"},{"key":"B142","doi-asserted-by":"publisher","DOI":"10.1038\/nrc.2017.77","article-title":"Tumour acidosis: from the passenger to the driver\u2019s seat","volume":"17","author":"Corbet","year":"2017","journal-title":"Nat Rev Cancer"},{"key":"B143","doi-asserted-by":"publisher","DOI":"10.1158\/1538-7445.AM2025-397","article-title":"Abstract 397: Combinatorial use of VHL and KEAP1-based PROTACs reveals unexpected synergy and hook effect relief","volume":"85","author":"Islam","year":"2025","journal-title":"Cancer Res"},{"key":"B144","doi-asserted-by":"publisher","DOI":"10.3762\/bjoc.22.49","article-title":"Advantages of PROTACs in achieving selective degradation of homologous protein families","volume":"22","author":"Yang","year":"2026","journal-title":"Beilstein J Org Chem"},{"key":"B145","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-0716-1665-9_13","article-title":"Methods for quantitative assessment of protein degradation","volume":"2365","author":"Nowak","year":"2021","journal-title":"Methods Mol Biol"},{"key":"B146","doi-asserted-by":"publisher","DOI":"10.1038\/s41589-018-0021-8","article-title":"The dTAG system for immediate and target-specific protein degradation","volume":"14","author":"Nabet","year":"2018","journal-title":"Nat Chem Biol"},{"key":"B147","doi-asserted-by":"publisher","DOI":"10.1021\/acschembio.9b00525","article-title":"Cellular resistance mechanisms to targeted protein degradation converge toward impairment of the engaged ubiquitin transfer pathway","volume":"14","author":"Ottis","year":"2019","journal-title":"ACS Chem Biol"},{"key":"B148","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-18-1129","article-title":"Acquired resistance to BET-PROTACs (proteolysis-targeting chimeras) caused by genomic alterations in core components of E3 ligase complexes","volume":"18","author":"Zhang","year":"2019","journal-title":"Mol Cancer Ther"},{"key":"B149","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-018-0005-8","article-title":"Revisiting the role of ABC transporters in multidrug-resistant cancer","volume":"18","author":"Robey","year":"2018","journal-title":"Nat Rev Cancer"},{"key":"B150","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.abn2707","article-title":"The drug efflux pump MDR1 promotes intrinsic and acquired resistance to PROTACs in cancer cells","volume":"15","author":"Kurimchak","year":"2022","journal-title":"Sci Signaling"},{"key":"B151","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-26-0251","article-title":"Molecular and structural basis of pan-resistance to BTK degraders and inhibitors","author":"Sievers","year":"2026","journal-title":"Cancer Discov"},{"key":"B152","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2026.03.009","article-title":"Assessing the suitability of deubiquitylases as substrates for targeted protein degradation","volume":"33","author":"Tong","year":"2026","journal-title":"Cell Chem Biol"},{"key":"B153","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2026.1844555","article-title":"Targeting the deubiquitinase USP28 in cancer: navigating context-dependent mechanisms and therapeutic resistance","volume":"17","author":"Luo","year":"2026","journal-title":"Front Immunol"},{"key":"B154","doi-asserted-by":"publisher","DOI":"10.4161\/auto.29409","article-title":"BAG3 induces the sequestration of proteasomal clients into cytoplasmic puncta: implications for a proteasome-to-autophagy switch","volume":"10","author":"Minoia","year":"2014","journal-title":"Autophagy"},{"key":"B155","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2026.115056","article-title":"Loss of DDI2 rewires proteostasis through CCN1-driven compensatory autophagy","volume":"29","author":"Hosseini","year":"2026","journal-title":"iScience"},{"key":"B156","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1038\/s41420-025-02355-6","article-title":"Role of TRIM24 in the regulation of proteasome-autophagy crosstalk in bortezomib-resistant mantle cell lymphoma","volume":"11","author":"Bouvier","year":"2025","journal-title":"Cell Death Discov"},{"key":"B157","doi-asserted-by":"publisher","first-page":"691","DOI":"10.1038\/s42003-025-08104-w","article-title":"Cellular parameters shaping pathways of targeted protein degradation","volume":"8","author":"Cardno","year":"2025","journal-title":"Commun Biol"},{"key":"B158","doi-asserted-by":"publisher","DOI":"10.1039\/D4CS00411F","article-title":"Proteolysis-targeting drug delivery system (ProDDS): Integrating targeted protein degradation concepts into formulation design","volume":"53","author":"Chen","year":"2024","journal-title":"Chem Soc Rev"},{"key":"B159","doi-asserted-by":"publisher","DOI":"10.1038\/d41573-024-00187-0","article-title":"The targeted protein degradation landscape","volume":"24","author":"Farley","year":"2024","journal-title":"Nat Rev Drug Discov"},{"key":"B160","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41587-024-02494-8","article-title":"Engineered platelets as targeted protein degraders and application to breast cancer models","volume":"43","author":"Chen","year":"2024","journal-title":"Nat Biotechnol"},{"key":"B161","doi-asserted-by":"publisher","DOI":"10.1039\/d3nr06059d","article-title":"Nano-PROTACs: state of the art and perspectives","volume":"16","author":"Zhong","year":"2024","journal-title":"Nanoscale"},{"key":"B162","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1007\/s10544-026-00832-y","article-title":"Mechanotherapeutic biomaterials: overcoming physical barriers to enhance intratumoral drug delivery in solid tumours","volume":"28","author":"Singh","year":"2026","journal-title":"BioMed Microdevices"},{"key":"B163","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.5c01632","article-title":"Rational design of PROTAC degraders and their spatiotemporal controlled delivery for enhanced tumor penetration and PD-L1 protein degradation","volume":"68","author":"Qi","year":"2025","journal-title":"J Med Chem"},{"key":"B164","doi-asserted-by":"publisher","DOI":"10.1016\/j.mtbio.2026.102767","article-title":"Ginsenoside RH2-functionalized liposomes enhanced BRD4-PROTAC delivery and antitumor efficacy via improved tumor targeting and ECM remodeling","volume":"36","author":"Wen","year":"2026","journal-title":"Mater Today Bio"},{"key":"B165","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2026.115922","article-title":"Targeted delivery of proteolysis-targeting chimeras (PROTAC) and molecular glue degraders (MGD)","volume":"236","author":"Banerjee","year":"2026","journal-title":"Adv Drug Delivery Rev"},{"key":"B166","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2026.104709","article-title":"Can PROTACs truly become oral drugs","volume":"31","author":"Alhafi","year":"2026","journal-title":"Drug Discov Today"},{"key":"B167","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.3c02332","article-title":"Beyond rule of five and PROTACs in modern drug discovery: polarity reducers, chameleonicity, and the evolving physicochemical landscape","volume":"67","author":"Price","year":"2024","journal-title":"J Med Chem"},{"key":"B168","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2014.08.013","article-title":"Oral druggable space beyond the rule of 5: insights from drugs and clinical candidates","volume":"21","author":"Doak","year":"2014","journal-title":"Chem Biol"},{"key":"B169","doi-asserted-by":"publisher","DOI":"10.1039\/d4md00854e","article-title":"In vitro and in vivo ADME of heterobifunctional degraders: a tailored approach to optimize DMPK properties of PROTACs","volume":"16","author":"Maurer","year":"2025","journal-title":"RSC Med Chem"},{"key":"B170","doi-asserted-by":"publisher","DOI":"10.1021\/acsmedchemlett.6c00043","article-title":"Evaluation of oral PROTAC guidelines: efflux ratio outweighs chameleonicity descriptors","volume":"17","author":"Le Manach","year":"2026","journal-title":"ACS Med Chem Lett"},{"key":"B171","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2025.07.020","article-title":"Photodynamic enhancement of PROTAC prodrug activation in hypoxic tumors","volume":"15","author":"Fu","year":"2025","journal-title":"Acta Pharm Sin B"},{"key":"B172","doi-asserted-by":"publisher","DOI":"10.1021\/acsami.6c05907","article-title":"Pretargeted PROTAC strategy enables precise tumor target degradation via self-assembling peptides","volume":"18","author":"Wu","year":"2026","journal-title":"ACS Appl Mater Interfaces"},{"key":"B173","doi-asserted-by":"publisher","DOI":"10.3390\/molecules29174048","article-title":"Stability evaluation and pharmacokinetic profiling of vepdegestrant in rodents using liquid chromatography-tandem mass spectrometry","volume":"29","author":"Choi","year":"2024","journal-title":"Molecules"},{"key":"B174","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.2c00877","article-title":"Linker-dependent folding rationalizes PROTAC cell permeability","volume":"65","author":"Poongavanam","year":"2022","journal-title":"J Med Chem"},{"key":"B175","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.2c00324","article-title":"Structural feature analyzation strategies toward discovery of orally bioavailable PROTACs of bruton\u2019s tyrosine kinase for the treatment of lymphoma","volume":"65","author":"Zhang","year":"2022","journal-title":"J Med Chem"},{"key":"B176","doi-asserted-by":"publisher","first-page":"998","DOI":"10.1016\/j.chembiol.2020.07.020","article-title":"PROTACs: an emerging therapeutic modality in precision medicine","volume":"27","author":"Nalawansha","year":"2020","journal-title":"Cell Chem Biol"},{"key":"B177","doi-asserted-by":"publisher","DOI":"10.1038\/nrc.2017.7","article-title":"Liquid biopsies come of age: towards implementation of circulating tumour DNA","volume":"17","author":"Wan","year":"2017","journal-title":"Nat Rev Cancer"},{"key":"B178","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-24-3612","article-title":"ctDNA clearance as an early indicator of improved clinical outcomes in advanced NSCLC treated with TKI: findings from an aggregate analysis of eight clinical trials","volume":"31","author":"Andrews","year":"2025","journal-title":"Clin Cancer Res"},{"key":"B179","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-025-03732-5","article-title":"Molecular determinants of sotorasib clinical efficacy in KRASG12C-mutated non-small-cell lung cancer","volume":"31","author":"Skoulidis","year":"2025","journal-title":"Nat Med"},{"key":"B180","doi-asserted-by":"publisher","first-page":"899","DOI":"10.1158\/1078-0432.CCR-24-2948","article-title":"Identification of candidate alterations mediating KRAS G12C inhibitor resistance in advanced colorectal and pancreatic cancers","volume":"31","author":"Jazieh","year":"2025","journal-title":"Clin Cancer Res"},{"key":"B181","doi-asserted-by":"publisher","DOI":"10.1126\/science.adi5798","article-title":"Kinase-impaired BTK mutations are susceptible to clinical-stage BTK and IKZF1\/3 degrader NX-2127","volume":"383","author":"Mukerji","year":"2024","journal-title":"Science"},{"key":"B182","doi-asserted-by":"publisher","DOI":"10.1177\/09622802251350457","article-title":"Using circulating tumor DNA as a novel biomarker of efficacy for dose-finding designs in oncology","volume":"34","author":"Chen","year":"2025","journal-title":"Stat Methods Med Res"},{"key":"B183","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.5c09630","article-title":"Cell-selective targeting chimeras (SelecTACB) for membrane protein degradation on B cells","volume":"147","author":"Yang","year":"2025","journal-title":"J Am Chem Soc"},{"key":"B184","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2026.153561","article-title":"Beyond the obvious: exploring the underappreciated dynamics and context-specific functions of lncRNAs","volume":"811","author":"Eladl","year":"2026","journal-title":"Biochem Biophys Res Commun"},{"key":"B185","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2026.153673","article-title":"Epitranscriptomic RNA modifications in human disease: cooperative networks, molecular mechanisms, and therapeutic opportunities","volume":"815","author":"Eladl","year":"2026","journal-title":"Biochem Biophys Res Commun"},{"key":"B186","doi-asserted-by":"publisher","first-page":"36397","DOI":"10.1038\/s41598-025-20519-3","article-title":"In-cell NMR spectra of chemically unmodified RNA at physiological temperature with extended lifetime through RNase inhibitor cocktail in living human cells","volume":"15","author":"Eladl","year":"2025","journal-title":"Sci Rep"},{"key":"B187","doi-asserted-by":"publisher","DOI":"10.1007\/s10334-025-01313-8","article-title":"In-cell NMR spectroscopy: advancements, applications, challenges, and future directions in structural biology","volume":"39","author":"Eladl","year":"2025","journal-title":"Magn Reson Mater Phys Biol Med"},{"key":"B188","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2026.1773130","article-title":"Dual-targeting phytochemicals ergosterol and quercetagetin implicate steroid metabolism-associated pathways in lung and liver cancer models","volume":"17","author":"Chen","year":"2026","journal-title":"Front Pharmacol"},{"key":"B189","doi-asserted-by":"publisher","DOI":"10.1016\/j.fitote.2026.107327","article-title":"Impact of arid-zone abiotic stress on phytochemical bioactivity: enhancing chemotherapeutic synergy in breast cancer and personalized therapeutic algorithms","volume":"192","author":"Abdelazim","year":"2026","journal-title":"Fitoterapia"},{"key":"B190","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.01.011","article-title":"Precision tumor recognition by T cells with combinatorial antigen-sensing circuits","volume":"164","author":"Roybal","year":"2016","journal-title":"Cell"},{"key":"B191","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202520774","article-title":"Split-deliver-click: tumor-specific protein degradation via \u201cAND\u201d logic-gated in-cell bioorthogonal clicking of PROTACs","volume":"65","author":"Dong","year":"2026","journal-title":"Angew Chem (Int Ed Engl)"},{"key":"B192","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-020-0347-5","article-title":"T cell-engaging therapies\u2014BiTEs and beyond","volume":"17","author":"Goebeler","year":"2020","journal-title":"Nat Rev Clin Oncol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1935909\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T13:47:30Z","timestamp":1788875250000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1935909\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,8]]},"references-count":192,"alternative-id":["10.3389\/fimmu.2026.1935909"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1935909","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,8]]},"article-number":"1935909"}}