{
  "abstract": "Antibody-drug conjugates (ADCs) have transitioned from clinically marginal agents into a defining therapeutic class for solid tumor oncology. In DESTINY-Breast03, trastuzumab deruxtecan achieved a four-fold progression-free survival advantage over trastuzumab emtansine, attributable not to antibody engineering but to the linker-payload axis: a cleavable peptide linker and a topoisomerase I payload with bystander activity. Sacituzumab govitecan extends the same logic to Trop-2-positive disease via extracellular payload release, and the framework now spans breast, urothelial, gynecologic, lung, gastric, and colorectal cancers, with enfortumab vedotin plus pembrolizumab displacing platinum chemotherapy as first-line therapy for urothelial cancer in EV-302 (median overall survival 31.5 versus 16.1 months). This review synthesizes ADC biology along three analytical axes. The mechanistic axis links each linker-payload-DAR configuration to a specific tumor-biology barrier: vascular limitation, which delivers approximately 0.1% of the administered dose to tumor tissue; the binding-site barrier, which concentrates exposure at the perivascular margin; and antigen mosaicism, which defeats internalization-dependent killing. The translational axis examines resistance as a coordinated failure across antigen modulation, trafficking, efflux, apoptotic execution, and lysosomal processing. The clinical axis traces the platform's migration toward earlier-line and curative-intent settings. We close by examining whether the ADC delivery architecture translates to precision immunosuppression in autoimmune disease, where the glucocorticoid receptor modulator ADC ABBV-154 met placebo-controlled efficacy endpoints in rheumatoid arthritis but was discontinued because its benefit-risk profile did not differentiate it from existing biologic therapies.",
  "abstract_shown": true,
  "affiliations": [
    "College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia",
    "Research Center, King Faisal Specialist Hospital and Research Center, Jeddah 21499, Saudi Arabia"
  ],
  "article_type": "review",
  "arxiv": null,
  "author_total": 11,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Ibraheem Masoud",
      "orcid": "0009-0006-9314-221X"
    },
    {
      "affs": [
        0
      ],
      "name": "Nada Saed Homod Al Shaer",
      "orcid": "0009-0009-1451-4217"
    },
    {
      "affs": [
        0
      ],
      "name": "Ahmad Masoud"
    },
    {
      "affs": [
        0
      ],
      "name": "Ahmad Al Jandali",
      "orcid": "0009-0004-9223-6826"
    },
    {
      "affs": [
        0
      ],
      "name": "Abdulrahman Aldahash",
      "orcid": "0009-0007-0100-0159"
    },
    {
      "affs": [
        0
      ],
      "name": "Abdullah Jabri",
      "orcid": "0009-0000-8048-9528"
    },
    {
      "affs": [
        0
      ],
      "name": "Mohamed Alsharif",
      "orcid": "0000-0003-0546-4210"
    },
    {
      "affs": [
        0
      ],
      "name": "Fareeha Arshad",
      "orcid": "0000-0002-6962-1927"
    },
    {
      "affs": [
        0
      ],
      "name": "Itika Arora",
      "orcid": "0000-0003-3761-4455"
    },
    {
      "affs": [
        1
      ],
      "name": "Mohammed Imran Khan",
      "orcid": "0000-0001-5832-5017"
    },
    {
      "affs": [
        0
      ],
      "name": "Ahmed Yaqinuddin",
      "orcid": "0000-0001-7536-910X"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/71r2t56szh1s7.bib",
  "cited_by": 5,
  "doi": "10.3390/ijms27125196",
  "fulltext_url": null,
  "id": "71r2t56szh1s7",
  "issns": [
    "1422-0067",
    "1661-6596"
  ],
  "landing_url": "https://doi.org/10.3390/ijms27125196",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2403|Monoclonal and Polyclonal Antibodies Research"
    ]
  ],
  "openalex": "W7163994406",
  "pdf_url": null,
  "pmcid": "PMC13300373",
  "pmid": "42352921",
  "published": "2026-06-09",
  "publisher": "Multidisciplinary Digital Publishing Institute",
  "ris": "https://research.draconitic.com/paper/71r2t56szh1s7.ris",
  "sources": [
    {
      "first_seen": "2026-11-07T13:20:53Z",
      "native_id": "W7163994406",
      "source": "openalex",
      "url": "https://doi.org/10.3390/ijms27125196"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2403|Monoclonal and Polyclonal Antibodies Research",
      "subfield": "immunology"
    }
  ],
  "title": "Antibody-Drug Conjugates in Solid Tumor Oncology and the Frontier of Precision Immunosuppression: A Mechanistic, Translational, and Clinical Review",
  "title_text": "Antibody-Drug Conjugates in Solid Tumor Oncology and the Frontier of Precision Immunosuppression: A Mechanistic, Translational, and Clinical Review",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T13:21:11Z",
  "url": "https://research.draconitic.com/paper/71r2t56szh1s7",
  "venue": "International Journal of Molecular Sciences",
  "versions": []
}