REVIEW article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
This article is part of the Research TopicAntibodyPlus Therapeutics in Oncology: Innovative Mechanisms, Therapeutic Strategies, and Clinical AdvancesView all 8 articles
Clinical Applications of Antibody-Drug Conjugates in Advanced Non-Small Cell Lung Cancer
Provisionally accepted
- 1Sichuan University West China Hospital Department of Thoracic Surgery, Chengdu, China
- 2Yuxi Traditional Chinese Medicine Hospital, Yuxi, China
- 3Sichuan Cancer Hospital, Chengdu, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
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)—engineered biotherapeutics comprising tumor-targeting antibodies conjugated to potent cytotoxic agents through optimized linkers—have 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‑H3 in advanced NSCLC. We critically assess efficacy outcomes, safety profiles, predictive biomarkers, and toxicity management strategies— particularly 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‑generation 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.
Keywords: Antibody–drug conjugates, Cancer, clinical application, NSCLC, targeted therapy
Received: 13 Jan 2026; Accepted: 29 Jan 2026.
Copyright: © 2026 Guo, Xu, Li, Guo, Lin, Pu and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Qiang Pu
Guosong Wang
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.