{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:56:23Z","timestamp":1786978583027,"version":"build-2736575974"},"reference-count":88,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Antibody\u2013drug conjugates (ADCs) have matured from a technically challenging concept into an established therapeutic platform across hematologic and solid malignancies. By linking a monoclonal antibody to a potent cytotoxic payload, ADCs seek to increase tumor-directed drug delivery while limiting systemic exposure; however, clinical performance depends on much more than target expression. Target accessibility, antigen density and heterogeneity, internalization, intracellular trafficking, linker stability, payload properties, drug-to-antibody ratio, bystander effect, tumor penetration, and host-tissue handling jointly shape efficacy and toxicity. This review provides a clinician-oriented assessment of the contemporary ADC landscape and the principal biologic and pharmacologic determinants of benefit. We discuss signature toxicities, including interstitial lung disease and ocular injury, and summarize evolving mechanisms of resistance and biomarker development. Particular emphasis is placed on three translational problems that are becoming increasingly important as ADCs move into earlier lines and overlapping disease settings: dose optimization beyond the maximum tolerated dose, sequencing across targets and payload classes, and biologically rational combination strategies. We also present a conceptual Sequential Tumor Attack Model as a hypothesis-generating framework for tumor-access priming, ADC-mediated cytotoxic injury, and immune amplification, while explicitly recognizing that the complete model has not been clinically validated. The future impact of ADCs will depend not only on next-generation constructs, but also on rigorous evidence for how these agents should be dosed, ordered, and combined in practice.<\/jats:p>","DOI":"10.3390\/cancers18162652","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T13:42:17Z","timestamp":1786974137000},"page":"2652","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Antibody\u2013Drug Conjugates in Contemporary Oncology: A Clinical Perspective on Dose Optimization, Sequencing, and Combination Strategies"],"prefix":"10.3390","volume":"18","author":[{"given":"Alexander","family":"Philipovskiy","sequence":"first","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Internal Medicine, Texas Tech University Health Sciences Center and UMC\/TLC2 Cancer Center, 602 Indiana Ave., Lubbock, TX 79415, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott","family":"Shurmur","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Texas Tech University Health Sciences Center, 3601 4th Street, Lubbock, TX 79430, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad Bilal","family":"Abid","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Internal Medicine, Texas Tech University Health Sciences Center and UMC\/TLC2 Cancer Center, 602 Indiana Ave., Lubbock, TX 79415, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,17]]},"reference":[{"key":"ref_1","unstructured":"Himmelweit, F. (1960). Experimental Researches on Specific Therapy: On Immunity with special Reference to the Relationship between Distribution and Action of Antigens. The Collected Papers of Paul Ehrlich, Pergamon. The Harben Lectures for 1907 of the Royal Institute of Public Health."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Chen, B., Zheng, X., Wu, J., Chen, G., Yu, J., Xu, Y., Wu, W.K.K., Tse, G.M.K., To, K.F., and Kang, W. (2025). Antibody\u2013drug conjugates in cancer therapy: Current landscape, challenges, and future directions. Mol. Cancer, 24.","DOI":"10.1186\/s12943-025-02489-2"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"197","DOI":"10.12793\/tcp.2025.33.e21","article-title":"A review of clinical pharmacology considerations in antibody-drug conjugates approved by the US Food and Drug Administration between 2000 and 2025","volume":"33","author":"Koo","year":"2025","journal-title":"Transl. Clin. Pharmacol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1038\/s41417-023-00701-3","article-title":"The target atlas for antibody-drug conjugates across solid cancers","volume":"31","author":"Fang","year":"2023","journal-title":"Cancer Gene Ther."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Wang, R., Hu, B., Pan, Z., Mo, C., Zhao, X., Liu, G., Hou, P., Cui, Q., Xu, Z., and Wang, W. (2025). Antibody\u2013Drug Conjugates (ADCs): Current and future biopharmaceuticals. J. Hematol. Oncol., 18.","DOI":"10.1186\/s13045-025-01704-3"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"oyaf331","DOI":"10.1093\/oncolo\/oyaf331","article-title":"Antibody drugs conjugates in non\u2013small cell lung cancer: Current status and challenges","volume":"30","author":"Syal","year":"2025","journal-title":"Oncologist"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Saleh, K., Raman, A., and Zanoni, M. (2025). Editorial: Antibody-drug conjugates in solid and hematologic malignancies. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1662653"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Zhang, F., and Li, S. (2025). Antibody-drug conjugates as game changers in bladder cancer: Current progress and future directions. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1591191"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"101978","DOI":"10.1016\/j.ijgc.2025.101978","article-title":"Antibody-drug conjugates in gynecologic cancer: Current landscape, clinical data, and emerging targets","volume":"35","author":"He","year":"2025","journal-title":"Int. J. Gynecol. Cancer"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Montalbano, M.C., Micillo, M., Deaglio, S., and Vaisitti, T. (2026). Antibody\u2013Drug Conjugates in Hematological Malignancies: Current Landscape and Future Perspectives. Int. J. Mol. Sci., 27.","DOI":"10.3390\/ijms27021025"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1177\/17588359251320285","article-title":"Efficacy of sacituzumab govitecan versus treatment of physician\u2019s choice in previously treated HR+ and HER2\u2212 mBC: A meta-analysis of TROPiCS-02 and EVER-132-002 trials","volume":"17","author":"Gluz","year":"2025","journal-title":"Ther. Adv. Med. Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1177\/17588359241248336","article-title":"TROPION-Breast03: A randomized phase III global trial of datopotamab deruxtecan \u00b1 durvalumab in patients with triple-negative breast cancer and residual invasive disease at surgical resection after neoadjuvant therapy","volume":"16","author":"Bardia","year":"2024","journal-title":"Ther. Adv. Med. Oncol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1080\/14796694.2026.2663956","article-title":"TROPION-Urothelial03: A phase II\/III study of datopotamab deruxtecan (Dato-DXd) for locally advanced or metastatic urothelial carcinoma","volume":"22","author":"Galsky","year":"2026","journal-title":"Futur. Oncol."},{"key":"ref_14","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\u2013Overexpressing Advanced Nonsquamous EGFR-Wildtype Non\u2013Small Cell Lung Cancer in the Phase II LUMINOSITY Trial","volume":"42","author":"Camidge","year":"2024","journal-title":"J. Clin. Oncol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1962","DOI":"10.1158\/1078-0432.CCR-25-3216","article-title":"Efficacy and Safety of Belantamab Mafodotin with Bortezomib plus Dexamethasone in Patients with Relapsed\/Refractory Multiple Myeloma: The DREAMM-6 Arm B Trial","volume":"32","author":"Popat","year":"2026","journal-title":"Clin. Cancer Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"105019","DOI":"10.1016\/j.critrevonc.2025.105019","article-title":"Trastuzumab deruxtecan: Redefining precision oncology across HER2-driven cancers","volume":"217","author":"Jalali","year":"2025","journal-title":"Crit. Rev. Oncol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"100849","DOI":"10.1016\/j.medj.2025.100849","article-title":"Antibody-drug conjugates: Current challenges and innovative solutions for precision cancer therapy","volume":"6","author":"Zhou","year":"2025","journal-title":"Med"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"102742","DOI":"10.1016\/j.xcrm.2026.102742","article-title":"Antibody-drug conjugates in breast cancer: Progress and future directions","volume":"7","author":"Newman","year":"2026","journal-title":"Cell Rep. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2011","DOI":"10.1158\/1078-0432.CCR-23-3738","article-title":"FDA Approval Summary: Enfortumab Vedotin plus Pembrolizumab for Cisplatin-Ineligible Locally Advanced or Metastatic Urothelial Carcinoma","volume":"30","author":"Maguire","year":"2024","journal-title":"Clin. Cancer Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1136\/ijgc-2024-005401","article-title":"Mirvetuximab soravtansine in folate receptor alpha (FR\u03b1)\u2013high platinum-resistant ovarian cancer: Final overall survival and post hoc sequence of therapy subgroup results from the SORAYA trial","volume":"34","author":"Coleman","year":"2024","journal-title":"Int. J. Gynecol. Cancer"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1056\/NEJMoa2508668","article-title":"Trastuzumab Deruxtecan plus Pertuzumab for HER2-Positive Metastatic Breast Cancer","volume":"394","author":"Tolaney","year":"2026","journal-title":"N. Engl. J. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1056\/NEJMoa2312117","article-title":"Enfortumab Vedotin and Pembrolizumab in Untreated Advanced Urothelial Cancer","volume":"390","author":"Powles","year":"2024","journal-title":"N. Engl. J. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.annonc.2025.10.019","article-title":"Neoadjuvant trastuzumab deruxtecan alone or followed by paclitaxel, trastuzumab, and pertuzumab for high-risk HER2-positive early breast cancer (DESTINY-Breast11): A randomised, open-label, multicentre, phase III trial","volume":"37","author":"Harbeck","year":"2025","journal-title":"Ann. Oncol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1056\/NEJMoa2514661","article-title":"Trastuzumab Deruxtecan in Residual HER2-Positive Early Breast Cancer","volume":"394","author":"Loibl","year":"2026","journal-title":"N. Engl. J. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1056\/NEJMoa2115304","article-title":"Polatuzumab Vedotin in Previously Untreated Diffuse Large B-Cell Lymphoma","volume":"386","author":"Tilly","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1529","DOI":"10.1056\/NEJMoa2028485","article-title":"Sacituzumab Govitecan in Metastatic Triple-Negative Breast Cancer","volume":"384","author":"Bardia","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1016\/S0140-6736(23)01245-X","article-title":"Overall survival with sacituzumab govitecan in hormone receptor-positive and human epidermal growth factor receptor 2-negative metastatic breast cancer (TROPiCS-02): A randomised, open-label, multicentre, phase 3 trial","volume":"402","author":"Rugo","year":"2023","journal-title":"Lancet"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1200\/JCO.23.02005","article-title":"Efficacy and Safety of Trastuzumab Deruxtecan in Patients with HER2-Expressing Solid Tumors: Primary Results From the DESTINY-PanTumor02 Phase II Trial","volume":"42","author":"Makker","year":"2024","journal-title":"J. Clin. Oncol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"4125","DOI":"10.1007\/s12325-024-02975-x","article-title":"Efficacy of Trastuzumab Deruxtecan in HER2-Expressing Solid Tumors by Enrollment HER2 IHC Status: Post Hoc Analysis of DESTINY-PanTumor02","volume":"41","author":"Oaknin","year":"2024","journal-title":"Adv. Ther."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2110","DOI":"10.1056\/NEJMoa2407086","article-title":"Trastuzumab Deruxtecan after Endocrine Therapy in Metastatic Breast Cancer","volume":"391","author":"Bardia","year":"2024","journal-title":"N. Engl. J. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1056\/NEJMoa2115022","article-title":"Trastuzumab Deruxtecan versus Trastuzumab Emtansine for Breast Cancer","volume":"386","author":"Kim","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"4852","DOI":"10.1200\/JCO.23.01361","article-title":"Trastuzumab Deruxtecan in Patients with HER2-Mutant Metastatic Non\u2013Small-Cell Lung Cancer: Primary Results From the Randomized, Phase II DESTINY-Lung02 Trial","volume":"41","author":"Goto","year":"2023","journal-title":"J. Clin. Oncol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1016\/S1470-2045(24)00140-2","article-title":"Trastuzumab deruxtecan in patients with solid tumours harbouring specific activating HER2 mutations (DESTINY-PanTumor01): An international, phase 2 study","volume":"25","author":"Li","year":"2024","journal-title":"Lancet Oncol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1056\/NEJMoa2313811","article-title":"Tisotumab Vedotin as Second- or Third-Line Therapy for Recurrent Cervical Cancer","volume":"391","author":"Vergote","year":"2024","journal-title":"N. Engl. J. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2162","DOI":"10.1056\/NEJMoa2309169","article-title":"Mirvetuximab Soravtansine in FR\u03b1-Positive, Platinum-Resistant Ovarian Cancer","volume":"389","author":"Moore","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1200\/JCO.24.00920","article-title":"Datopotamab Deruxtecan Versus Chemotherapy in Previously Treated Inoperable\/Metastatic Hormone Receptor\u2013Positive Human Epidermal Growth Factor Receptor 2\u2013Negative Breast Cancer: Primary Results From TROPION-Breast01","volume":"43","author":"Bardia","year":"2025","journal-title":"J. Clin. Oncol."},{"key":"ref_37","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\u2013Small 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_38","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_39","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1056\/NEJMoa2405090","article-title":"Belantamab Mafodotin, Bortezomib, and Dexamethasone for Multiple Myeloma","volume":"391","author":"Hungria","year":"2024","journal-title":"N. Engl. J. Med."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Glassman, P.M. (2025). Pharmacokinetic and Pharmacodynamic Modeling of Antibody-Drug Conjugates. Cancers, 18.","DOI":"10.3390\/cancers18010005"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e202500262","DOI":"10.1002\/cmdc.202500262","article-title":"Linker Design for the Antibody Drug Conjugates: A Comprehensive Review","volume":"20","author":"Lei","year":"2025","journal-title":"ChemMedChem"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Sheyi, R., de la Torre, B.G., and Albericio, F. (2022). Linkers: An Assurance for Controlled Delivery of Antibody-Drug Conjugate. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14020396"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3889","DOI":"10.1016\/j.apsb.2021.03.042","article-title":"Antibody\u2013drug conjugates: Recent advances in linker chemistry","volume":"11","author":"Su","year":"2021","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Valsasina, B., Orsini, P., Terenghi, C., and Ocana, A. (2024). Present Scenario and Future Landscape of Payloads for ADCs: Focus on DNA-Interacting Agents. Pharmaceuticals, 17.","DOI":"10.3390\/ph17101338"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Mckertish, C.M., and Kayser, V. (2021). Advances and Limitations of Antibody Drug Conjugates for Cancer. Biomedicines, 9.","DOI":"10.3390\/biomedicines9080872"},{"key":"ref_46","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."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1158\/1535-7163.MCT-21-0580","article-title":"Cellular-Resolution Imaging of Bystander Payload Tissue Penetration from Antibody-Drug Conjugates","volume":"21","author":"Khera","year":"2021","journal-title":"Mol. Cancer Ther."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1038\/nbt.3212","article-title":"Reducing hydrophobicity of homogeneous antibody-drug conjugates improves pharmacokinetics and therapeutic index","volume":"33","author":"Lyon","year":"2015","journal-title":"Nat. Biotechnol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Mahmood, I. (2021). Clinical Pharmacology of Antibody-Drug Conjugates. Antibodies, 10.","DOI":"10.3390\/antib10020020"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1007\/s40265-022-01736-w","article-title":"Trastuzumab Deruxtecan-Induced Interstitial Lung Disease\/Pneumonitis in ERBB2-Positive Advanced Solid Malignancies: A Systematic Review","volume":"82","author":"Abuhelwa","year":"2022","journal-title":"Drugs"},{"key":"ref_51","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_52","doi-asserted-by":"crossref","unstructured":"Mao, K., Chen, P., Sun, H., Zhong, S., Zheng, H., and Xu, L. (2024). Ocular adverse events associated with antibody-drug conjugates in oncology: A pharmacovigilance study based on FDA adverse event reporting system (FAERS). Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1425617"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"102113","DOI":"10.1016\/j.eclinm.2023.102113","article-title":"Toxicity profile of antibody-drug conjugates in breast cancer: Practical considerations","volume":"62","author":"Verrazzo","year":"2023","journal-title":"eClinicalMedicine"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Nguyen, T.D., Bordeau, B.M., and Balthasar, J.P. (2023). Mechanisms of ADC Toxicity and Strategies to Increase ADC Tolerability. Cancers, 15.","DOI":"10.3390\/cancers15030713"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41523-025-00868-y","article-title":"Mechanisms of resistance to trastuzumab deruxtecan in breast cancer elucidated by multi-omic molecular profiling","volume":"12","author":"Sledge","year":"2025","journal-title":"npj Breast Cancer"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2110","DOI":"10.1038\/s41591-023-02478-2","article-title":"Trastuzumab deruxtecan in metastatic breast cancer with variable HER2 expression: The phase 2 DAISY trial","volume":"29","author":"Mosele","year":"2023","journal-title":"Nat. Med."},{"key":"ref_57","first-page":"1496","article-title":"Membranous NECTIN-4 Expression Frequently Decreases during Metastatic Spread of Urothelial Carcinoma and Is Associated with Enfortumab Vedotin Resistance","volume":"29","author":"Ralser","year":"2022","journal-title":"Clin. Cancer Res."},{"key":"ref_58","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":"2022","journal-title":"Cancer Commun."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Abelman, R.O., Wu, B., Spring, L.M., Ellisen, L.W., and Bardia, A. (2023). Mechanisms of Resistance to Antibody\u2013Drug Conjugates. Cancers, 15.","DOI":"10.3390\/cancers15041278"},{"key":"ref_60","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_61","doi-asserted-by":"crossref","first-page":"1148","DOI":"10.1016\/j.annonc.2021.06.002","article-title":"Biomarker analyses in the phase III ASCENT study of sacituzumab govitecan versus chemotherapy in patients with metastatic triple-negative breast cancer","volume":"32","author":"Bardia","year":"2021","journal-title":"Ann. Oncol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1093\/annonc\/mdv577","article-title":"Molecular imaging as a tool to investigate heterogeneity of advanced HER2-positive breast cancer and to predict patient outcome under trastuzumab emtansine (T-DM1): The ZEPHIR trial","volume":"27","author":"Gebhart","year":"2015","journal-title":"Ann. Oncol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1038\/s41523-023-00610-6","article-title":"Molecular imaging predicts lack of T-DM1 response in advanced HER2-positive breast cancer (final results of ZEPHIR trial)","volume":"10","author":"Mileva","year":"2024","journal-title":"npj Breast Cancer"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"105828","DOI":"10.1016\/j.esmoop.2025.105828","article-title":"Survival outcomes and the role of DNADX ctDNA testing in patients treated with sacituzumab govitecan for metastatic breast cancer","volume":"10","author":"Morganti","year":"2025","journal-title":"ESMO Open"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1097\/RLU.0000000000001820","article-title":"89Zr-Trastuzumab PET\/CT for Detection of Human Epidermal Growth Factor Receptor 2\u2013Positive Metastases in Patients with Human Epidermal Growth Factor Receptor 2\u2013Negative Primary Breast Cancer","volume":"42","author":"Ulaner","year":"2017","journal-title":"Clin. Nucl. Med."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1080\/14796694.2024.2434388","article-title":"Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer: A plain language summary of the DESTINY-Breast04 study","volume":"21","author":"Modi","year":"2025","journal-title":"Futur. Oncol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"673","DOI":"10.17305\/bb.2024.10641","article-title":"Tumor-type agnostic, targeted therapies make a new step forward: The first tumor-agnostic approval of a HER2-targeted therapy","volume":"24","author":"Vranic","year":"2024","journal-title":"Biomol. Biomed."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1002\/psp4.13141","article-title":"Population pharmacokinetics and exposure\u2013response analyses of polatuzumab vedotin in patients with previously untreated DLBCL from the POLARIX study","volume":"13","author":"Deng","year":"2024","journal-title":"CPT Pharmacomet. Syst. Pharmacol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1002\/psp4.13058","article-title":"Application of the model-informed drug development paradigm to datopotamab deruxtecan dose selection for late-stage development","volume":"13","author":"Lu","year":"2023","journal-title":"CPT Pharmacomet. Syst. Pharmacol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1002\/cpt.2291","article-title":"Exposure-Response Relationships in Patients with HER2-Positive Metastatic Breast Cancer and Other Solid Tumors Treated with Trastuzumab Deruxtecan","volume":"110","author":"Yin","year":"2021","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1278","DOI":"10.1002\/cpt.3383","article-title":"Population Pharmacokinetic Modeling and Exposure\u2013Response Analysis for the Antibody\u2013Drug Conjugate Enfortumab Vedotin in Locally Advanced or Metastatic Urothelial Carcinoma","volume":"116","author":"Zuo","year":"2024","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1038\/s41416-024-02766-9","article-title":"Efficacy of administration sequence: Sacituzumab Govitecan and Trastuzumab Deruxtecan in HER2-low metastatic breast cancer","volume":"131","author":"Poumeaud","year":"2024","journal-title":"Br. J. Cancer"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1038\/s41523-025-00748-5","article-title":"Multicenter retrospective cohort study of the sequential use of the antibody-drug conjugates (ADCs) trastuzumab deruxtecan (T-DXd) and sacituzumab govitecan (SG) in patients with HER2-low metastatic breast cancer (MBC)","volume":"11","author":"Huppert","year":"2025","journal-title":"npj Breast Cancer"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"e957","DOI":"10.1093\/oncolo\/oyae055","article-title":"Optimal Sequential Strategies for Antibody-Drug Conjugate in Metastatic Breast Cancer: Evaluating Efficacy and Cross-Resistance","volume":"29","author":"Chen","year":"2024","journal-title":"Oncologist"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"e2400898","DOI":"10.1200\/PO-24-00898","article-title":"Sequential Antibody-Drug Conjugate Therapy in Patients with Metastatic Breast Cancer Treated with Sacituzumab Govitecan and Trastuzumab Deruxtecan","volume":"9","author":"Mai","year":"2025","journal-title":"JCO Precis. Oncol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1966","DOI":"10.1158\/1078-0432.CCR-24-2771","article-title":"TOP1 Mutations and Cross-Resistance to Antibody\u2013Drug Conjugates in Patients with Metastatic Breast Cancer","volume":"31","author":"Abelman","year":"2025","journal-title":"Clin. Cancer Res."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1454","DOI":"10.1158\/1078-0432.CCR-25-3321","article-title":"Payload Diversification Overcomes Resistance and Guides Sequential Antibody\u2013Drug Conjugate Therapy in Breast Cancer","volume":"32","author":"Rampa","year":"2026","journal-title":"Clin. Cancer Res."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1186\/s13058-025-02094-7","article-title":"Comparison of trastuzumab deruxtecan and sacituzumab govitecan in HER2-negative metastatic breast cancer: A large real-world data analysis","volume":"27","author":"Sledge","year":"2025","journal-title":"Breast Cancer Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1016\/S1470-2045(20)30465-4","article-title":"Trastuzumab emtansine plus atezolizumab versus trastuzumab emtansine plus placebo in previously treated, HER2-positive advanced breast cancer (KATE2): A phase 2, multicentre, randomised, double-blind trial","volume":"21","author":"Emens","year":"2020","journal-title":"Lancet Oncol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.ygyno.2023.01.020","article-title":"Safety and efficacy of mirvetuximab soravtansine, a folate receptor alpha (FR\u03b1)-targeting antibody-drug conjugate (ADC), in combination with bevacizumab in patients with platinum-resistant ovarian cancer","volume":"170","author":"Gilbert","year":"2023","journal-title":"Gynecol. Oncol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"103688","DOI":"10.1016\/j.jtho.2026.103688","article-title":"Datopotamab Deruxtecan Plus Pembrolizumab with or Without Platinum-Based Chemotherapy for Advanced or Metastatic NSCLC: The Phase Ib TROPION-Lung02 Trial","volume":"21","author":"Levy","year":"2026","journal-title":"J. Thorac. Oncol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1056\/NEJMoa2508959","article-title":"Sacituzumab Govitecan plus Pembrolizumab for Advanced Triple-Negative Breast Cancer","volume":"394","author":"Tolaney","year":"2026","journal-title":"N. Engl. J. Med."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1965","DOI":"10.1016\/j.apsb.2024.01.009","article-title":"Bispecific antibody drug conjugates: Making 1 + 1 > 2","volume":"14","author":"Gu","year":"2024","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1007\/s00280-025-04863-9","article-title":"Recent advances in bispecific antibody-drug conjugates for breast cancer therapy","volume":"96","author":"Ji","year":"2026","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1016\/S1470-2045(24)00159-1","article-title":"BL-B01D1, a first-in-class EGFR\u2013HER3 bispecific antibody\u2013drug conjugate, in patients with locally advanced or metastatic solid tumours: A first-in-human, open-label, multicentre, phase 1 study","volume":"25","author":"Ma","year":"2024","journal-title":"Lancet Oncol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"4459","DOI":"10.1158\/1078-0432.CCR-21-1353","article-title":"Unmasking New Promises: Expanding the Antigen Landscape for Antibody\u2013Drug Conjugates","volume":"27","author":"Oberoi","year":"2021","journal-title":"Clin. Cancer Res."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"4521","DOI":"10.1158\/1078-0432.CCR-21-0194","article-title":"Phase I, First-in-Human Study of the Probody Therapeutic CX-2029 in Adults with Advanced Solid Tumor Malignancies","volume":"27","author":"Johnson","year":"2021","journal-title":"Clin. Cancer Res."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Smith, F.D., Pierce, R.H., Thisted, T., and van der Horst, E.H. (2023). Conditionally Active, pH-Sensitive Immunoregulatory Antibodies Targeting VISTA and CTLA-4 Lead an Emerging Class of Cancer Therapeutics. 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