{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T21:49:44Z","timestamp":1793742584980,"version":"4.6.1"},"reference-count":198,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T00:00:00Z","timestamp":1771372800000},"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>Lung cancer remains the leading cause of cancer-related incidence and mortality worldwide, with non-small cell lung cancer (NSCLC) constituting the majority of cases. Current treatment modalities are constrained by significant limitations: conventional chemotherapy exhibits poor tumor selectivity and systemic toxicity, while monoclonal antibodies frequently demonstrate inadequate therapeutic efficacy. Antibody-drug conjugates (ADCs)\u2014engineered biotherapeutics comprising tumor-targeting antibodies conjugated to potent cytotoxic agents through optimized linkers\u2014have emerged as a transformative strategy to address these therapeutic challenges in advanced NSCLC. This review systematically examines the structural architecture, developmental evolution, and mechanistic foundations of ADCs, with a focused evaluation of clinical evidence supporting ADCs targeting HER2, TROP2, c-MET, HER3, CEACAM5, and B7\u2212H3 in advanced NSCLC. We critically assess efficacy outcomes, safety profiles, predictive biomarkers, and toxicity management strategies\u2014particularly regarding interstitial lung disease, hematologic toxicities, and neuropathic adverse events. Key clinical challenges including tumor heterogeneity, therapeutic resistance, biomarker heterogeneity, and patient stratification are analyzed. Furthermore, we highlight emerging therapeutic approaches such as next\u2212generation ADC design, novel linker-payload systems, bispecific platforms, and rational combination strategies with targeted and immunotherapeutic agents. Collectively, these developments position ADCs as promising precision oncology tools capable of reshaping treatment paradigms and improving clinical outcomes in advanced NSCLC.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1787148","type":"journal-article","created":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T06:54:23Z","timestamp":1771397663000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Clinical applications of antibody-drug conjugates in advanced non-small cell lung cancer"],"prefix":"10.3389","volume":"17","author":[{"given":"Hai","family":"Guo","sequence":"first","affiliation":[{"name":"Department of Thoracic Surgery, West China Hospital, Sichuan University","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongcai","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Yuxi Traditional Chinese Medicine 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