{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T12:25:12Z","timestamp":1788265512234,"version":"build-2803163510"},"reference-count":168,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Curr. Issues Mol. Biol.","CIMB"],"abstract":"<jats:p>Lung cancer is currently the most frequently diagnosed malignancy worldwide, accounting for approximately 12.4% of all cancers and, despite major advances in molecularly targeted therapies and immunotherapy, represents the leading cause of cancer-related mortality. In recent years, antibody\u2013drug conjugates (ADCs) have emerged as a novel therapeutic strategy, combining the specificity of monoclonal antibodies with the potent cytotoxic activity of highly active payloads to selectively target tumor cells while limiting systemic toxicity. This narrative review summarizes the current role of ADCs in lung cancer, with particular focus on their structural components, mechanisms of action, and the biological features that determine treatment efficacy. We discuss the rationale for targeting established and emerging antigens in non-small cell and small cell lung cancer, including HER2, TROP2, c-MET, HER3, CEACAM5, DLL3, and other promising targets currently under clinical investigation. The principal mechanisms of primary and acquired resistance are also reviewed, including antigen modulation, altered intracellular trafficking, lysosomal dysfunction, drug efflux, tumor microenvironment-mediated immune suppression, and intratumor heterogeneity. In addition, we provide an overview of the safety profile of ADCs, highlighting the most clinically relevant adverse events and their underlying biological mechanisms. We also examine the evolving landscape of predictive biomarkers beyond antigen expression, including genomic, transcriptomic, proteomic, and liquid biopsy-based approaches, together with emerging spatial and single-cell technologies that may improve patient selection. Finally, we discuss future directions in the field, including novel payloads, next-generation linker technologies, bispecific ADCs, combination strategies, and personalized ADC development. Overall, ADCs are rapidly reshaping the therapeutic landscape of lung cancer. Continued optimization of drug design, biomarker-driven patient selection, and a deeper understanding of resistance mechanisms will be essential to fully realize their clinical potential.<\/jats:p>","DOI":"10.3390\/cimb48090868","type":"journal-article","created":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T16:54:42Z","timestamp":1787763282000},"page":"868","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Antibody\u2013Drug Conjugates in Lung Cancer: Promise, Progress, and Persistent Challenges"],"prefix":"10.3390","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5485-6056","authenticated-orcid":false,"given":"Panagiotis","family":"Paliogiannis","sequence":"first","affiliation":[{"name":"Department of Medicine, Surgery and Pharmacy, University of Sassari, Viale San Pietro 43, 07100 Sassari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgia","family":"Fara","sequence":"additional","affiliation":[{"name":"Burn Center, University Hospital (AOU) of Sassari, Via Enrico De Nicola 39, 07100 Sassari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8396-0968","authenticated-orcid":false,"given":"Angelo","family":"Zinellu","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, University of Sassari, Viale San Pietro 43, 07100 Sassari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5330-572X","authenticated-orcid":false,"given":"Alessandro Giuseppe","family":"Fois","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Pharmacy, University of Sassari, Viale San Pietro 43, 07100 Sassari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4350-2276","authenticated-orcid":false,"given":"Giuseppe","family":"Palmieri","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Pharmacy, University of Sassari, Viale San Pietro 43, 07100 Sassari, Italy"},{"name":"Unit of Cancer Genetics, Institute of Genetic and Biomedical Research (IRGB), National Research Council (CNR), Traversa La Crucca n. 3, 07100 Sassari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,26]]},"reference":[{"key":"ref_1","first-page":"e70090","article-title":"Global cancer statistics 2024: GLOBOCAN estimates of incidence and mortality worldwide for 34 cancers in 186 countries","volume":"76","author":"Sung","year":"2026","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1016\/j.chest.2021.12.655","article-title":"Distribution, risk factors, and temporal trends for lung cancer incidence and mortality: A global analysis","volume":"161","author":"Huang","year":"2022","journal-title":"Chest"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Inamura, K. (2017). Lung cancer: Understanding its molecular pathology and the 2015 WHO classification. Front. Oncol., 7.","DOI":"10.3389\/fonc.2017.00193"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1016\/S2213-2600(24)00428-4","article-title":"Estimated worldwide variation and trends in incidence of lung cancer by histological subtype in 2022 and over time: A population-based study","volume":"13","author":"Luo","year":"2025","journal-title":"Lancet Respir. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"8","DOI":"10.5334\/aogh.2419","article-title":"Global epidemiology of lung cancer","volume":"85","author":"Barta","year":"2019","journal-title":"Ann. Glob. Health"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Paliogiannis, P., Colombino, M., Sini, M.C., Manca, A., Casula, M., Palomba, G., Pisano, M., Doneddu, V., Zinellu, A., and Santeufemia, D. (2022). Global prognostic impact of driver genetic alterations in patients with lung adenocarcinoma: A real-life study. BMC Pulm. Med., 22.","DOI":"10.1186\/s12890-021-01803-0"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1111\/1759-7714.15170","article-title":"Observed and relative survival trends of lung cancer: A systematic review of population-based cancer registration data","volume":"15","author":"Bi","year":"2024","journal-title":"Thorac. Cancer"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1186\/2049-6958-8-45","article-title":"Lung cancer epidemiology in North Sardinia, Italy","volume":"8","author":"Paliogiannis","year":"2013","journal-title":"Multidiscip. Respir. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"102862","DOI":"10.1016\/j.critrevonc.2019.102862","article-title":"Diagnosis and treatment of early and locally advanced non-small-cell lung cancer: The 2019 AIOM (Italian Association of Medical Oncology) clinical practice guidelines","volume":"148","author":"Passiglia","year":"2020","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Fois, S.S., Paliogiannis, P., Zinellu, A., Fois, A.G., Cossu, A., and Palmieri, G. (2021). Molecular epidemiology of the main druggable genetic alterations in non-small cell lung cancer. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22020612"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"104925","DOI":"10.1016\/j.critrevonc.2025.104925","article-title":"KRAS mutations in non-small cell lung cancer: Translational aspects, current therapies and challenges for future research","volume":"215","author":"Colombino","year":"2025","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Colombino, M., Paliogiannis, P., Cossu, A., Santeufemia, D.A., Sardinian Lung Cancer (SLC) Study Group, Sini, M.C., Casula, M., Palomba, G., Manca, A., and Pisano, M. (2019). EGFR, KRAS, BRAF, ALK, and cMET genetic alterations in 1440 Sardinian patients with lung adenocarcinoma. BMC Pulm. Med., 19.","DOI":"10.1186\/s12890-019-0964-x"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3495","DOI":"10.3390\/curroncol31060258","article-title":"A review of immunotherapy in non-small-cell lung cancer","volume":"31","author":"Capella","year":"2024","journal-title":"Curr. Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Putzu, C., Canova, S., Paliogiannis, P., Lobrano, R., Sala, L., Cortinovis, D.L., and Colonese, F. (2023). Duration of immunotherapy in non-small cell lung cancer survivors: A lifelong commitment?. Cancers, 15.","DOI":"10.3390\/cancers15030689"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Xiang, Y., Liu, X., Wang, Y., Zheng, D., Meng, Q., Jiang, L., Yang, S., Zhang, S., Zhang, X., and Liu, Y. (2024). Mechanisms of resistance to targeted therapy and immunotherapy in non-small cell lung cancer: Promising strategies to overcoming challenges. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1366260"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1016\/S0140-6736(24)01029-8","article-title":"New promises and challenges in the treatment of advanced non-small-cell lung cancer","volume":"404","author":"Meyer","year":"2024","journal-title":"Lancet"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1038\/nrd.2016.268","article-title":"Strategies and challenges for the next generation of antibody-drug conjugates","volume":"16","author":"Beck","year":"2017","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Ponziani, S., Di Vittorio, G., Pitari, G., Cimini, A.M., Ardini, M., Gentile, R., Iacobelli, S., Sala, G., Capone, E., and Flavell, D.J. (2020). Antibody-drug conjugates: The new frontier of chemotherapy. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21155510"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e70699","DOI":"10.1002\/mco2.70699","article-title":"Antibody-drug conjugates in oncology: Principles, clinical development, and future directions","volume":"7","author":"Cheng","year":"2026","journal-title":"MedComm"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/s40164-024-00493-8","article-title":"Drug conjugates for the treatment of lung cancer: From drug discovery to clinical practice","volume":"13","author":"Zhou","year":"2024","journal-title":"Exp. Hematol. Oncol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1097\/CCO.0000000000001200","article-title":"Antibody-drug conjugates in lung cancer: Current landscape and future perspectives","volume":"38","author":"Chen","year":"2026","journal-title":"Curr. Opin. Oncol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1038\/nrc2394","article-title":"Paul Ehrlich\u2019s magic bullet concept: 100 years of progress","volume":"8","author":"Strebhardt","year":"2008","journal-title":"Nat. Rev. Cancer"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2089","DOI":"10.1158\/2159-8290.CD-24-0708","article-title":"The journey of antibody-drug conjugates: Lessons learned from 40 years of development","volume":"14","author":"Colombo","year":"2024","journal-title":"Cancer Discov."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Zaytsev, D., Girshova, L., Ivanov, V., Budaeva, I., Motorin, D., Badaev, R., Mirolubova, J., Grobovenko, E., Chitanava, T., and Zaykova, E. (2020). Rapid efficacy of gemtuzumab ozogamicin in refractory AML patients with pulmonary and kidney failure. Biology, 9.","DOI":"10.3390\/biology9020028"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1186\/s13045-025-01704-3","article-title":"Antibody-drug conjugates (ADCs): Current and future biopharmaceuticals","volume":"18","author":"Wang","year":"2025","journal-title":"J. Hematol. Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1038\/s41573-023-00709-2","article-title":"Antibody-drug conjugates come of age in oncology","volume":"22","author":"Dumontet","year":"2023","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2","DOI":"10.32604\/or.2026.078000","article-title":"Engineering the future of ADCs in non-small cell lung cancer","volume":"34","author":"Kim","year":"2026","journal-title":"Oncol. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1038\/s41571-023-00850-2","article-title":"Exploring the next generation of antibody-drug conjugates","volume":"21","author":"Tsuchikama","year":"2024","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Wu, G., Yuan, Z., Chen, M., Tang, X., Wang, F., and Zhang, D. (2026). Antibody-drug conjugates (ADCs): A review of structural design, technological evolution, and future perspectives. Molecules, 31.","DOI":"10.3390\/molecules31071180"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Parslow, A.C., Parakh, S., Lee, F.T., Gan, H.K., and Scott, A.M. (2016). Antibody-drug conjugates for cancer therapy. Biomedicines, 4.","DOI":"10.3390\/biomedicines4030014"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Riccardi, F., Dal Bo, M., Macor, P., and Toffoli, G. (2023). A comprehensive overview on antibody-drug conjugates: From the conceptualization to cancer therapy. Front. Pharmacol., 14.","DOI":"10.3389\/fphar.2023.1274088"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3577","DOI":"10.1007\/s11095-015-1729-8","article-title":"Internalization, trafficking, intracellular processing and actions of antibody-drug conjugates","volume":"32","author":"Xu","year":"2015","journal-title":"Pharm. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e00225","DOI":"10.1042\/BSR20150089","article-title":"Antibody-drug conjugates as novel anti-cancer chemotherapeutics","volume":"35","author":"Peters","year":"2015","journal-title":"Biosci. Rep."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e1395127","DOI":"10.1080\/2162402X.2017.1395127","article-title":"Antibody structure and engineering considerations for the design and function of Antibody Drug Conjugates (ADCs)","volume":"7","author":"Hoffmann","year":"2017","journal-title":"Oncoimmunology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1038\/s41571-021-00470-8","article-title":"Unlocking the potential of antibody-drug conjugates for cancer therapy","volume":"18","author":"Drago","year":"2021","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3526","DOI":"10.1007\/s11095-015-1657-7","article-title":"Current ADC linker chemistry","volume":"32","author":"Jain","year":"2015","journal-title":"Pharm. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3889","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":"ref_38","doi-asserted-by":"crossref","unstructured":"Kostova, V., D\u00e9sos, P., Starck, J.B., and Kotschy, A. (2021). The chemistry behind ADCs. Pharmaceuticals, 14.","DOI":"10.3390\/ph14050442"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"4361","DOI":"10.1039\/C8CS00676H","article-title":"Cleavable linkers in antibody-drug conjugates","volume":"48","author":"Bargh","year":"2019","journal-title":"Chem. Soc. Rev."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"4025","DOI":"10.1016\/j.apsb.2023.06.015","article-title":"Antibody-drug conjugates: Recent advances in payloads","volume":"13","author":"Wang","year":"2023","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"116709","DOI":"10.1016\/j.ejmech.2024.116709","article-title":"Antibody-drug conjugates for targeted cancer therapy: Recent advances in potential payloads","volume":"276","author":"Xi","year":"2024","journal-title":"Eur. J. Med. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Li, X., Liu, J., Meng, Y., Li, J., Zhao, J., Liu, D., and Zhang, X. (2026). Frontiers in antibody-drug conjugates: Mechanisms, design innovations, and clinical applications in targeted cancer therapy. Pharmaceuticals, 19.","DOI":"10.3390\/ph19020324"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"4392","DOI":"10.1021\/jm060319f","article-title":"Semisynthetic maytansine analogues for the targeted treatment of cancer","volume":"49","author":"Widdison","year":"2006","journal-title":"J. Med. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Jang, J.Y., Kim, D., Lee, N.K., Im, E., and Kim, N.D. (2025). Antibody-drug conjugates powered by deruxtecan: Innovations and challenges in oncology. Int. J. Mol. Sci., 26.","DOI":"10.20944\/preprints202506.1081.v1"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"10540","DOI":"10.1074\/jbc.M510026200","article-title":"Lysosomal trafficking and cysteine protease metabolism confer target-specific cytotoxicity by peptide-linked anti-CD30-auristatin conjugates","volume":"281","author":"Sutherland","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.neo.2020.12.001","article-title":"Quantifying ADC bystander payload penetration with cellular resolution using pharmacodynamic mapping","volume":"23","author":"Khera","year":"2021","journal-title":"Neoplasia"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"104979","DOI":"10.1016\/j.critrevonc.2025.104979","article-title":"Bystander effect in antibody-drug conjugates: Navigating the fine line in tumor heterogeneity","volume":"216","author":"Wang","year":"2025","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1007\/s11912-022-01266-4","article-title":"Bystander effect of antibody-drug conjugates: Fact or fiction?","volume":"24","author":"Giugliano","year":"2022","journal-title":"Curr. Oncol. Rep."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2514050","DOI":"10.1080\/2162402X.2025.2514050","article-title":"Patritumab deruxtecan induces immunogenic cell death","volume":"14","author":"Forveille","year":"2025","journal-title":"Oncoimmunology"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e1565859","DOI":"10.1080\/2162402X.2019.1565859","article-title":"Maytansine-bearing antibody-drug conjugates induce in vitro hallmarks of immunogenic cell death selectively in antigen-positive target cells","volume":"8","author":"Bauzon","year":"2019","journal-title":"Oncoimmunology"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1158\/2326-6066.CIR-15-0120","article-title":"Fc-receptor interactions regulate both cytotoxic and immunomodulatory therapeutic antibody effector functions","volume":"3","author":"DiLillo","year":"2015","journal-title":"Cancer Immunol. Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"6469","DOI":"10.1038\/sj.onc.1210477","article-title":"The oncogene HER2: Its signaling and transforming functions and its role in human cancer pathogenesis","volume":"26","author":"Moasser","year":"2007","journal-title":"Oncogene"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1038\/35052073","article-title":"Untangling the ErbB signalling network","volume":"2","author":"Yarden","year":"2001","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_54","unstructured":"(2026, June 30). NCCN Guidelines. Available online: https:\/\/www.nccn.org\/guidelines\/guidelines-detail?category=1&id=1450."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"28989","DOI":"10.18632\/oncotarget.25615","article-title":"The emergence of trophoblast cell-surface antigen 2 (TROP-2) as a novel cancer target","volume":"9","author":"Goldenberg","year":"2018","journal-title":"Oncotarget"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1186\/1477-7819-10-53","article-title":"Significance of EpCAM and TROP2 expression in non-small cell lung cancer","volume":"10","author":"Pak","year":"2012","journal-title":"World J. Surg. Oncol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"103","DOI":"10.21037\/tlcr-2025-1-1467","article-title":"From biology to the clinic: Research evidence and therapeutic advances of TROP2-targeted antibody-drug conjugates in small cell lung cancer","volume":"15","author":"Lu","year":"2026","journal-title":"Transl. Lung Cancer Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1038\/s41568-018-0002-y","article-title":"Known and novel roles of the MET oncogene in cancer: A coherent approach to targeted therapy","volume":"18","author":"Comoglio","year":"2018","journal-title":"Nat. Rev. Cancer"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"S7","DOI":"10.1177\/1758834011422556","article-title":"An overview of the c-MET signaling pathway","volume":"3","author":"Organ","year":"2011","journal-title":"Ther. Adv. Med. Oncol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"17588359241290733","DOI":"10.1177\/17588359241290733","article-title":"Targeting the MET gene: Unveiling therapeutic opportunities in immunotherapy within the tumor immune microenvironment of non-small cell lung cancer","volume":"16","author":"Ye","year":"2024","journal-title":"Ther. Adv. Med. Oncol."},{"key":"ref_61","first-page":"242","article-title":"Dysregulation of the Met pathway in non-small cell lung cancer: Implications for drug targeting and resistance","volume":"4","author":"Sacco","year":"2015","journal-title":"Transl. Lung Cancer Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2963","DOI":"10.1007\/s13346-024-01564-3","article-title":"Progress of antibody-drug conjugates (ADCs) targeting c-Met in cancer therapy; insights from clinical and preclinical studies","volume":"14","author":"Mer","year":"2024","journal-title":"Drug Deliv. Transl. Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1186\/s13046-020-01711-x","article-title":"MET and RON receptor tyrosine kinases in colorectal adenocarcinoma: Molecular features as drug targets and antibody-drug conjugates for therapy","volume":"39","author":"Yao","year":"2020","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1038\/s41698-025-01144-9","article-title":"MET (c-Met) protein overexpression is an emerging protein biomarker in non-small cell lung cancer","volume":"9","author":"Tsao","year":"2025","journal-title":"npj Precis. Oncol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"100790","DOI":"10.1016\/j.esmoop.2023.100790","article-title":"Targeting HER3 for cancer treatment: A new horizon for an old target","volume":"8","author":"Uliano","year":"2023","journal-title":"ESMO Open"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1007\/s40259-016-0205-2","article-title":"HER3 as a therapeutic target in cancer","volume":"31","author":"Karachaliou","year":"2017","journal-title":"BioDrugs"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1158\/1078-0432.CCR-21-3359","article-title":"HER3 augmentation via blockade of EGFR\/AKT signaling enhances anticancer activity of HER3-targeting patritumab deruxtecan in EGFR-mutated non-small cell lung cancer","volume":"28","author":"Yonesaka","year":"2022","journal-title":"Clin. Cancer Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"70","DOI":"10.3747\/co.2007.109","article-title":"Recent advances in the tumour biology of the GPI-anchored carcinoembryonic antigen family members CEACAM5 and CEACAM6","volume":"14","author":"Chan","year":"2007","journal-title":"Curr. Oncol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"107356","DOI":"10.1016\/j.lungcan.2023.107356","article-title":"The search for therapeutic targets in lung cancer: Preclinical and human studies of carcinoembryonic antigen-related cell adhesion molecule 5 expression and its associated molecular landscape","volume":"184","author":"Lefebvre","year":"2023","journal-title":"Lung Cancer"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"300060520959478","DOI":"10.1177\/0300060520959478","article-title":"CEACAM5 stimulates the progression of non-small-cell lung cancer by promoting cell proliferation and migration","volume":"48","author":"Zhang","year":"2020","journal-title":"J. Int. Med. Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"2984","DOI":"10.1111\/cas.15017","article-title":"Delta-like canonical Notch ligand 3 as a potential therapeutic target in malignancies: A brief overview","volume":"112","author":"Matsuo","year":"2021","journal-title":"Cancer Sci."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"302ra136","DOI":"10.1126\/scitranslmed.aac9459","article-title":"A DLL3-targeted antibody-drug conjugate eradicates high-grade pulmonary neuroendocrine tumor-initiating cells in vivo","volume":"7","author":"Saunders","year":"2015","journal-title":"Sci. Transl. Med."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1007\/s12672-024-01171-1","article-title":"Antibody-drug conjugates treatment of small cell lung cancer: Advances in clinical research","volume":"15","author":"Meng","year":"2024","journal-title":"Discov. Oncol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"153","DOI":"10.36401\/JIPO-24-34","article-title":"B7 Homolog 4 (B7-H4)-directed agents in oncology clinical trials: A review","volume":"8","author":"Phipps","year":"2025","journal-title":"J. Immunother. Precis. Oncol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"4511","DOI":"10.1158\/1078-0432.CCR-20-3757","article-title":"First-in-human study of PF-06647020 (Cofetuzumab Pelidotin), an antibody-drug conjugate targeting protein tyrosine kinase 7, in advanced solid tumors","volume":"27","author":"Maitland","year":"2021","journal-title":"Clin. Cancer Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1038\/bjc.2016.428","article-title":"Giving AXL the axe: Targeting AXL in human malignancy","volume":"116","author":"Gay","year":"2017","journal-title":"Br. J. Cancer"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1038\/s41420-024-02239-1","article-title":"Therapeutic advances in the targeting of ROR1 in hematological cancers","volume":"10","author":"Tigu","year":"2024","journal-title":"Cell Death Discov."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"396","DOI":"10.2119\/2007-00040.Taylor","article-title":"The emerging role of the LIV-1 subfamily of zinc transporters in breast cancer","volume":"13","author":"Taylor","year":"2007","journal-title":"Mol. Med."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"3003","DOI":"10.1158\/0008-5472.CAN-15-1313","article-title":"Enfortumab vedotin antibody-drug conjugate targeting nectin-4 is a highly potent therapeutic agent in multiple preclinical cancer models","volume":"76","author":"Satpayev","year":"2016","journal-title":"Cancer Res."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1248\/cpb.c18-00744","article-title":"The latest research and development into the antibody-drug conjugate, [fam-] trastuzumab deruxtecan (DS-8201a), for HER2 cancer therapy","volume":"67","author":"Nakada","year":"2019","journal-title":"Chem. Pharm. Bull."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"e431766","DOI":"10.1200\/EDBK_431766","article-title":"Unlocking the potential: Biomarkers of response to antibody-drug conjugates","volume":"44","author":"Ascione","year":"2024","journal-title":"Am. Soc. Clin. Oncol. Educ. Book"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1814","DOI":"10.1016\/j.jtho.2025.07.129","article-title":"Final analysis results and patient-reported outcomes from DESTINY-Lung02-A dose-blinded, randomized, phase 2 study of trastuzumab deruxtecan in patients with HER2-mutant metastatic NSCLC","volume":"20","author":"Goto","year":"2025","journal-title":"J. Thorac. Oncol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"e2543107","DOI":"10.1001\/jamanetworkopen.2025.43107","article-title":"Trastuzumab deruxtecan for ERBB2-mutant metastatic non-small cell lung cancer with or without brain metastases: A secondary analysis of randomized clinical trials","volume":"8","author":"Planchard","year":"2025","journal-title":"JAMA Netw. Open"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"103651","DOI":"10.1016\/j.jtho.2026.103651","article-title":"Systemic and intracranial efficacy and safety of trastuzumab deruxtecan in patients with HER2-mutant NSCLC across treatment lines: Evidence from the TRACER\/HERTras real-world cohort","volume":"24","author":"Illini","year":"2026","journal-title":"J. Thorac. Oncol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/S1470-2045(24)00064-0","article-title":"Trastuzumab deruxtecan in patients with metastatic non-small-cell lung cancer (DESTINY-Lung01): Primary results of the HER2-overexpressing cohorts from a single-arm, phase 2 trial","volume":"25","author":"Smit","year":"2024","journal-title":"Lancet Oncol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"2532","DOI":"10.1200\/JCO.2018.77.9777","article-title":"Ado-trastuzumab emtansine for patients with HER2-mutant lung cancers: Results from a phase II basket trial","volume":"36","author":"Li","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.jtho.2017.10.032","article-title":"A phase II study of trastuzumab emtansine in HER2-positive non-small cell lung cancer","volume":"13","author":"Hotta","year":"2018","journal-title":"J. Thorac. Oncol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1200\/JCO-24-01544","article-title":"Datopotamab deruxtecan versus docetaxel for previously treated advanced or metastatic non-small cell lung cancer: The randomized, open-label phase III TROPION-Lung01 study","volume":"43","author":"Ahn","year":"2025","journal-title":"J. Clin. Oncol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1669","DOI":"10.1016\/j.jtho.2025.06.002","article-title":"A pooled analysis of datopotamab deruxtecan in patients with EGFR-mutated NSCLC","volume":"20","author":"Ahn","year":"2025","journal-title":"J. Thorac. Oncol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"2607","DOI":"10.1016\/S0140-6736(26)00968-2","article-title":"Sacituzumab tirumotecan plus pembrolizumab versus pembrolizumab in PD-L1-positive advanced non-small-cell lung cancer (OptiTROP-Lung05): Interim analysis of a randomised, open-label, phase 3 trial","volume":"407","author":"Xiong","year":"2026","journal-title":"Lancet"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"3000","DOI":"10.1200\/JCO.24.00720","article-title":"Telisotuzumab vedotin monotherapy in patients with previously treated c-Met protein-overexpressing advanced nonsquamous EGFR-wildtype non-small cell lung cancer in the phase II LUMINOSITY trial","volume":"42","author":"Camidge","year":"2024","journal-title":"J. Clin. Oncol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"5363","DOI":"10.1200\/JCO.23.01476","article-title":"HERTHENA-Lung01, a phase II trial of patritumab deruxtecan (HER3-DXd) in epidermal growth factor receptor-mutated non-small-cell lung cancer after epidermal growth factor receptor tyrosine kinase inhibitor therapy and platinum-based chemotherapy","volume":"41","author":"Yu","year":"2023","journal-title":"J. Clin. Oncol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"969","DOI":"10.2217\/fon-2023-0602","article-title":"HERTHENA-Lung02: Phase III study of patritumab deruxtecan in advanced EGFR-mutated NSCLC after a third-generation EGFR TKI","volume":"20","author":"Mok","year":"2024","journal-title":"Future Oncol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"108492","DOI":"10.1016\/j.lungcan.2025.108492","article-title":"A phase 1b study of cofetuzumab pelidotin monotherapy in patients with PTK7-expressing recurrent non-small cell lung cancer","volume":"202","author":"Cho","year":"2025","journal-title":"Lung Cancer"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1016\/j.annonc.2026.01.009","article-title":"Izalontamab brengitecan (Iza-bren; BL-B01D1), a first-in-class EGFR-HER3 bispecific antibody-drug conjugate, for patients with EGFR-mutated NSCLC: Pooled analysis of phase I and phase II trials","volume":"37","author":"Hong","year":"2026","journal-title":"Ann. Oncol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1200\/JCO-25-02142","article-title":"Ifinatamab deruxtecan in patients with extensive-stage small cell lung cancer: Primary analysis of the phase II IDeate-Lung01 trial","volume":"44","author":"Rudin","year":"2026","journal-title":"J. Clin. Oncol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"2898","DOI":"10.1038\/s41591-026-04452-0","article-title":"SEZ6-targeting antibody-drug conjugate ABBV-706 in advanced small cell lung cancer and solid tumors: A phase 1 trial","volume":"32","author":"Byers","year":"2026","journal-title":"Nat. Med."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"114747","DOI":"10.1016\/j.jconrel.2026.114747","article-title":"The emerging role of antibody-drug conjugates in EGFR-mutant non-small cell lung cancer with acquired resistance to third-generation EGFR tyrosine kinase inhibitors","volume":"393","author":"Zhang","year":"2026","journal-title":"J. Control. Release"},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Cheng, Y., Yuan, X., Tian, Q., Huang, X., Chen, Y., Pu, Y., Long, H., Xu, M., Ji, Y., and Xie, J. (2022). Preclinical profiles of SKB264, a novel anti-TROP2 antibody conjugated to topoisomerase inhibitor, demonstrated promising antitumor efficacy compared to IMMU-132. Front. Oncol., 12, Erratum in Front. Oncol. 2023, 13, 1334938. https:\/\/doi.org\/10.3389\/fonc.2023.1334938.","DOI":"10.3389\/fonc.2023.1334938"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"5097","DOI":"10.1158\/1078-0432.CCR-15-2822","article-title":"DS-8201a, a novel HER2-targeting ADC with a novel DNA topoisomerase I inhibitor, demonstrates a promising antitumor efficacy with differentiation from T-DM1","volume":"22","author":"Ogitani","year":"2016","journal-title":"Clin. Cancer Res."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1007\/s00262-012-1369-3","article-title":"Proposed mechanism of off-target toxicity for antibody-drug conjugates driven by mannose receptor uptake","volume":"62","author":"Gorovits","year":"2013","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1186\/s13045-025-01720-3","article-title":"Treatment-related adverse events of antibody drug-conjugates in clinical trials","volume":"18","author":"Tan","year":"2025","journal-title":"J. Hematol. Oncol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1056\/NEJMoa2112431","article-title":"Trastuzumab deruxtecan in HER2-mutant non-small-cell lung cancer","volume":"386","author":"Li","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.1200\/JCO-24-01349","article-title":"Datopotamab deruxtecan in advanced or metastatic non-small cell lung cancer with actionable genomic alterations: Results from the phase II TROPION-Lung05 Study","volume":"43","author":"Sands","year":"2025","journal-title":"J. Clin. Oncol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"103960","DOI":"10.1016\/j.critrevonc.2023.103960","article-title":"Incidence of antibody-drug conjugates-related pneumonitis in patients with solid tumors: A systematic review and meta-analysis","volume":"184","author":"Zhu","year":"2023","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"100554","DOI":"10.1016\/j.esmoop.2022.100554","article-title":"Pooled analysis of drug-related interstitial lung disease and\/or pneumonitis in nine trastuzumab deruxtecan monotherapy studies","volume":"7","author":"Powell","year":"2022","journal-title":"ESMO Open"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1873","DOI":"10.1001\/jamaoncol.2021.3595","article-title":"Interstitial lung disease induced by anti-ERBB2 antibody-drug conjugates: A review","volume":"7","author":"Tarantino","year":"2021","journal-title":"JAMA Oncol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1158\/1535-7163.MCT-24-0267","article-title":"Potential mechanisms of interstitial lung disease induced by antibody-drug conjugates based on quantitative analysis of drug distribution","volume":"24","author":"Koganemaru","year":"2025","journal-title":"Mol. Cancer Ther."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1007\/s12672-024-01705-7","article-title":"Advancements in research and clinical management of interstitial lung injury associated with ADC drugs administration in breast cancer","volume":"15","author":"Zhu","year":"2024","journal-title":"Discov. Oncol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1097\/CM9.0000000000003149","article-title":"Cancer therapy-related interstitial lung disease","volume":"138","author":"Zhou","year":"2025","journal-title":"Chin. Med. J."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"102720","DOI":"10.1016\/j.ctrv.2024.102720","article-title":"Clinical management, monitoring, and prophylaxis of adverse events of special interest associated with datopotamab deruxtecan","volume":"125","author":"Heist","year":"2024","journal-title":"Cancer Treat. Rev."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"3054","DOI":"10.1002\/cncr.35475","article-title":"Clinical best practices in interdisciplinary management of human epidermal growth factor receptor 2 antibody-drug conjugates-induced interstitial lung disease\/pneumonitis: An expert consensus in China","volume":"130","author":"Xu","year":"2024","journal-title":"Cancer"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1080\/17425255.2022.2162383","article-title":"Clinical best practices in optimal monitoring, early diagnosis, and effective management of antibody-drug conjugate-induced interstitial lung disease or pneumonitis: A multidisciplinary team approach in Singapore","volume":"18","author":"Yong","year":"2022","journal-title":"Expert. Opin. Drug Metab. Toxicol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"7006","DOI":"10.1158\/1078-0432.CCR-17-0696","article-title":"Defective cyclin B1 induction in trastuzumab-emtansine (T-DM1) acquired resistance in HER2-positive breast cancer","volume":"23","author":"Sabbaghi","year":"2017","journal-title":"Clin. Cancer Res."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1034","DOI":"10.1158\/1078-0432.CCR-19-1768","article-title":"Inhibition of MDR1 overcomes resistance to brentuximab vedotin in Hodgkin lymphoma","volume":"26","author":"Chen","year":"2020","journal-title":"Clin. Cancer Res."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"15336","DOI":"10.1073\/pnas.1102855108","article-title":"Exosomal evasion of humoral immunotherapy in aggressive B-cell lymphoma modulated by ATP-binding cassette transporter A3","volume":"108","author":"Aung","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1002\/jcp.22773","article-title":"Potential role of HER2-overexpressing exosomes in countering trastuzumab-based therapy","volume":"227","author":"Ciravolo","year":"2012","journal-title":"J. Cell. Physiol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1093\/jnci\/djk134","article-title":"Expression of p95HER2, a truncated form of the HER2 receptor, and response to anti-HER2 therapies in breast cancer","volume":"99","author":"Scaltriti","year":"2007","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"17","DOI":"10.47248\/chp2502040017","article-title":"Navigating solid tumor heterogeneity: The promise and challenges of antibody-drug conjugates","volume":"2","author":"Duhon","year":"2025","journal-title":"Cancer Heterog. Plast."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1186\/s13058-017-0900-z","article-title":"Endophilin A2 promotes HER2 internalization and sensitivity to trastuzumab-based therapy in HER2-positive breast cancers","volume":"19","author":"Baldassarre","year":"2017","journal-title":"Breast Cancer Res."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1038\/s41416-019-0635-y","article-title":"Mechanisms of resistance to trastuzumab emtansine (T-DM1) in HER2-positive breast cancer","volume":"122","author":"Hunter","year":"2020","journal-title":"Br. J. Cancer"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1158\/1535-7163.MCT-17-0403","article-title":"Caveolae-mediated endocytosis as a novel mechanism of resistance to trastuzumab emtansine (T-DM1)","volume":"17","author":"Sung","year":"2018","journal-title":"Mol. Cancer Ther."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1021\/acs.bioconjchem.7b00013","article-title":"Improved lysosomal trafficking can modulate the potency of antibody drug conjugates","volume":"28","author":"DeVay","year":"2017","journal-title":"Bioconjug. Chem."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"4639","DOI":"10.1158\/0008-5472.CAN-16-3127","article-title":"Resistance to the antibody-drug conjugate T-DM1 is based in a reduction in lysosomal proteolytic activity","volume":"77","author":"Arribas","year":"2017","journal-title":"Cancer Res."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.drup.2015.11.004","article-title":"Lysosomes as mediators of drug resistance in cancer","volume":"24","author":"Zhitomirsky","year":"2016","journal-title":"Drug Resist. Updat."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"5329","DOI":"10.1158\/0008-5472.CAN-15-1610","article-title":"SLC46A3 is required to transport catabolites of noncleavable antibody maytansine conjugates from the lysosome to the cytoplasm","volume":"75","author":"Hamblett","year":"2015","journal-title":"Cancer Res."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"21141","DOI":"10.18632\/oncotarget.24975","article-title":"Esophageal cancer cells resistant to T-DM1 display alterations in cell adhesion and the prostaglandin pathway","volume":"9","author":"Sauveur","year":"2018","journal-title":"Oncotarget"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"7296","DOI":"10.1038\/sj.onc.1206935","article-title":"Mechanisms of resistance to topoisomerase I-targeting drugs","volume":"22","author":"Rasheed","year":"2003","journal-title":"Oncogene"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1158\/1535-7163.MCT-20-0351","article-title":"Resistance to pyrrolobenzodiazepine dimers is associated with SLFN11 downregulation and can be reversed through inhibition of ATR","volume":"20","author":"Mao","year":"2021","journal-title":"Mol. Cancer Ther."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1002\/cac2.12387","article-title":"Resistance to antibody-drug conjugates in breast cancer: Mechanisms and solutions","volume":"43","author":"Chen","year":"2023","journal-title":"Cancer Commun."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1016\/j.apsb.2024.12.036","article-title":"Resistance to antibody-drug conjugates: A review","volume":"15","author":"Li","year":"2025","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1038\/nrm2163","article-title":"The spindle-assembly checkpoint in space and time","volume":"8","author":"Musacchio","year":"2007","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1038\/s42003-021-01653-w","article-title":"Plk1, upregulated by HIF-2, mediates metastasis and drug resistance of clear cell renal cell carcinoma","volume":"4","author":"Dufies","year":"2021","journal-title":"Commun. Biol."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1016\/j.cub.2006.04.043","article-title":"Mitotic checkpoint slippage in humans occurs via cyclin B destruction in the presence of an active checkpoint","volume":"16","author":"Brito","year":"2006","journal-title":"Curr. Biol."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1016\/j.exphem.2009.03.002","article-title":"Deficient activation of Bak and Bax confers resistance to gemtuzumab ozogamicin-induced apoptotic cell death in AML","volume":"37","author":"Haag","year":"2009","journal-title":"Exp. Hematol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"2191","DOI":"10.1158\/0008-5472.CAN-08-1056","article-title":"Trastuzumab-induced HER reprogramming in \u201cresistant\u201d breast carcinoma cells","volume":"69","author":"Narayan","year":"2009","journal-title":"Cancer Res."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1038\/nature11249","article-title":"Widespread potential for growth-factor-driven resistance to anticancer kinase inhibitors","volume":"487","author":"Wilson","year":"2012","journal-title":"Nature"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.semcancer.2019.07.017","article-title":"Acquired resistance to cancer immunotherapy: Role of tumor-mediated immunosuppression","volume":"65","author":"Saleh","year":"2020","journal-title":"Semin. Cancer Biol."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"2686","DOI":"10.1158\/0008-5472.CAN-16-2854","article-title":"Antibody-drug conjugates bearing pyrrolobenzodiazepine or tubulysin payloads are immunomodulatory and synergize with multiple immunotherapies","volume":"77","author":"Harper","year":"2017","journal-title":"Cancer Res."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1186\/s12943-026-02663-0","article-title":"Immunogenic cell death as a cornerstone for combination therapies with immune checkpoint blockade","volume":"25","author":"Niu","year":"2026","journal-title":"Mol. Cancer"},{"key":"ref_141","first-page":"103555","article-title":"Loss of payload sensitivity and other mechanisms of resistance to T-DXd in HER2-mutant NSCLC: Implications for subsequent responsiveness to HER2 TKIs","volume":"21","author":"Nilsson","year":"2026","journal-title":"J. Thorac. Oncol."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1007\/s40265-026-02331-z","article-title":"Antibody-drug conjugates in non-small cell lung cancer","volume":"86","author":"Zullo","year":"2026","journal-title":"Drugs"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1056\/NEJMoa2203690","article-title":"Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer","volume":"387","author":"Modi","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"5005","DOI":"10.2147\/DDDT.S489234","article-title":"Current status and future prospects of TROP-2 ADCs in lung cancer treatment","volume":"18","author":"Li","year":"2024","journal-title":"Drug Des. Devel. Ther."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1038\/s41379-021-00919-2","article-title":"Digital pathology and artificial intelligence in translational medicine and clinical practice","volume":"35","author":"Baxi","year":"2022","journal-title":"Mod. Pathol."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"269","DOI":"10.32074\/1591-951X-1100","article-title":"The routine use of a digital tool for the tumor cell fraction quantification in molecular pathology: An international validation of QuANTUM","volume":"117","author":"Capitoli","year":"2025","journal-title":"Pathologica"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1186\/s40364-024-00653-2","article-title":"DNA damage response in breast cancer and its significant role in guiding novel precise therapies","volume":"12","author":"Li","year":"2024","journal-title":"Biomark. Res."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1038\/s41523-025-00829-5","article-title":"Antibody-drug conjugates in breast cancer: Mechanisms of resistance and future therapeutic perspectives","volume":"11","author":"Valle","year":"2025","journal-title":"npj Breast Cancer"},{"key":"ref_149","doi-asserted-by":"crossref","unstructured":"Fadda, G.M., Lobrano, R., Casula, M., Pisano, M., Pazzola, A., Cossu, A., Palmieri, G., and Paliogiannis, P. (2022). Liquid biopsy in the oncological management of a histologically undiagnosed lung carcinoma: A case report. J. Pers. Med., 12.","DOI":"10.3390\/jpm12111874"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"187","DOI":"10.3892\/mmr.2015.3347","article-title":"Impact of tissue type and content of neoplastic cells of samples on the quality of epidermal growth factor receptor mutation analysis among patients with lung adenocarcinoma","volume":"12","author":"Paliogiannis","year":"2015","journal-title":"Mol. Med. Rep."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"2803","DOI":"10.1080\/14796694.2025.2542051","article-title":"Recent advances in liquid biopsy for precision oncology: Emerging biomarkers and clinical applications in lung cancer","volume":"21","author":"Pepe","year":"2025","journal-title":"Future Oncol."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1080\/14737159.2025.2534961","article-title":"Smaller, cheaper, faster: Where next for liquid biopsies?","volume":"25","author":"Gristina","year":"2025","journal-title":"Expert Rev. Mol. Diagn."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1080\/14737140.2025.2549538","article-title":"Innovation in next-generation sequencing in non-small cell lung cancer diagnostics","volume":"25","author":"Scimone","year":"2025","journal-title":"Expert Rev. Anticancer Ther."},{"key":"ref_154","doi-asserted-by":"crossref","unstructured":"Casula, M., Pisano, M., Paliogiannis, P., Colombino, M., Sini, M.C., Zinellu, A., Santeufemia, D., Manca, A., Casula, S., and Tore, S. (2023). Comparison between three different techniques for the detection of EGFR mutations in liquid biopsies of patients with advanced stage lung adenocarcinoma. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24076410"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"100462","DOI":"10.1016\/j.jlb.2026.100462","article-title":"Harmonizing definitions in liquid biopsy: A terminology framework by the international society of liquid biopsy","volume":"12","author":"Gandara","year":"2026","journal-title":"J. Liq. Biopsy"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1038\/s41571-025-01003-3","article-title":"Emerging clinical applications of single-cell RNA sequencing in oncology","volume":"22","author":"Boxer","year":"2025","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1186\/s13045-025-01722-1","article-title":"Application of single-cell and spatial omics in deciphering cellular hallmarks of cancer drug response and resistance","volume":"18","author":"Cheng","year":"2025","journal-title":"J. Hematol. Oncol."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1007\/s10555-025-10304-z","article-title":"Spatial omics: Applications and utility in profiling the tumor microenvironment","volume":"44","author":"See","year":"2025","journal-title":"Cancer Metastasis Rev."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"17588359241309461","DOI":"10.1177\/17588359241309461","article-title":"Innovative payloads for ADCs in cancer treatment: Moving beyond the selective delivery of chemotherapy","volume":"17","author":"Izzo","year":"2025","journal-title":"Ther. Adv. Med. Oncol."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"1588","DOI":"10.1021\/acs.bioconjchem.6b00117","article-title":"Understanding how the stability of the thiol-maleimide linkage impacts the pharmacokinetics of lysine-linked antibody-maytansinoid conjugates","volume":"27","author":"Ponte","year":"2016","journal-title":"Bioconjug. Chem."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1021\/acs.bioconjchem.6c00154","article-title":"Peptide tag-nology for preparation of site-specific antibody-drug conjugates","volume":"37","author":"Ringaci","year":"2026","journal-title":"Bioconjug. Chem."},{"key":"ref_162","doi-asserted-by":"crossref","unstructured":"Yu, X., Ke, X., Tang, Y., Tang, T., Ni, Y., Guo, L., Cui, Y., Mei, Y., Xu, G., and Wu, G. (2026). Advancements in dual-load antibody-drug conjugates and challenges with quality analysis. Pharmaceuticals, 19.","DOI":"10.20944\/preprints202604.2053.v1"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1186\/s13045-025-01752-9","article-title":"Overcoming resistance to antibody-drug conjugates: From mechanistic insights to cutting-edge strategies","volume":"18","author":"Zhou","year":"2025","journal-title":"J. Hematol. Oncol."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.bcp.2015.12.008","article-title":"Combining antibody-drug conjugates and immune-mediated cancer therapy: What to expect?","volume":"102","author":"Gerber","year":"2016","journal-title":"Biochem. Pharmacol."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"1819","DOI":"10.1056\/NEJMoa2511065","article-title":"Sevabertinib in advanced HER2-mutant non-small-cell lung cancer","volume":"393","author":"Le","year":"2025","journal-title":"N. Engl. J. Med."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"2321","DOI":"10.1056\/NEJMoa2503704","article-title":"Zongertinib in previously treated HER2-mutant non-small-cell lung cancer","volume":"392","author":"Heymach","year":"2025","journal-title":"N. Engl. J. Med."},{"key":"ref_167","doi-asserted-by":"crossref","unstructured":"Chen, Y., Zhang, Y., Tian, C., Li, Z., and Guo, G. (2026). Evolution and recent advances in antibody-drug conjugate therapy for lung cancer: A comprehensive systematic review based on the Trialtrove database (inception to July 1, 2025). Front. Oncol., 16.","DOI":"10.3389\/fonc.2026.1793949"},{"key":"ref_168","doi-asserted-by":"crossref","unstructured":"Lin, H., Ma, X., Zhu, X., and Zhong, L. (2025). The potential of antibody-drug conjugates in immunotherapy for non-small cell lung cancer: Current progress and future. Front. Oncol., 15.","DOI":"10.3389\/fonc.2025.1630056"}],"container-title":["Current Issues in Molecular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1467-3045\/48\/9\/868\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T12:09:15Z","timestamp":1788264555000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1467-3045\/48\/9\/868"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,26]]},"references-count":168,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["cimb48090868"],"URL":"https:\/\/doi.org\/10.3390\/cimb48090868","relation":{},"ISSN":["1467-3045"],"issn-type":[{"value":"1467-3045","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,26]]}}}