The DOI matches its Crossref record; 248 of the 248 references it cites were found in a registry or an index.
Exploring the next generation of antibody–drug conjugates
Abstract
Antibody-drug conjugates (ADCs) are a promising cancer treatment modality that enables the selective delivery of highly cytotoxic payloads to tumours. However, realizing the full potential of this platform necessitates innovative molecular designs to tackle several clinical challenges such as drug resistance, tumour heterogeneity and treatment-related adverse effects. Several emerging ADC formats exist, including bispecific ADCs, conditionally active ADCs (also known as probody-drug conjugates), immune-stimulating ADCs, protein-degrader ADCs and dual-drug ADCs, and each offers unique capabilities for tackling these various challenges. For example, probody-drug conjugates can enhance tumour specificity, whereas bispecific ADCs and dual-drug ADCs can address resistance and heterogeneity with enhanced activity. The incorporation of immune-stimulating and protein-degrader ADCs, which have distinct mechanisms of action, into existing treatment strategies could enable multimodal cancer treatment. Despite the promising outlook, the importance of patient stratification and biomarker identification cannot be overstated for these emerging ADCs, as these factors are crucial to identify patients who are most likely to derive benefit. As we continue to deepen our understanding of tumour biology and refine ADC design, we will edge closer to developing truly effective and safe ADCs for patients with treatment-refractory cancers. In this Review, we highlight advances in each ADC component (the monoclonal antibody, payload, linker and conjugation chemistry) and provide more-detailed discussions on selected examples of emerging novel ADCs of each format, enabled by engineering of one or more of these components.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Thirteen FDA-approved ADCs are currently on the market, with over 200 ADCs in various stages of clinical development (Table 1)6,8,9.”
From The evolving landscape of antibody-drug conjugates (ADCs) for treatment of prostate cancer (2025) · cites this paper as [8]
In the citing paper
“To date, 11 ADCs have been Food and Drug Administration (FDA)-approved for 20 specific indications”
From Current and emerging concepts for systemic treatment of metastatic colorectal cancer (2025) · cites this paper as [59]
Citations
Cites
Tumour heterogeneity and resistance to cancer therapies
Dagogo-Jack, I., & Shaw, A. T. (2018) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2017.166 · Cited by 3,846
PROTAC targeted protein degraders: the past is prologue
Békés, M., Langley, D. R., & Crews, C. M. (2022) · Nature Reviews Drug Discovery · doi:10.1038/s41573-021-00371-6 · Cited by 3,395
Strategies and challenges for the next generation of antibody–drug conjugates
Beck, A., Goetsch, L., Dumontet, C., & Corvaïa, N. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2016.268 · Cited by 2,271
Blinatumomab versus Chemotherapy for Advanced Acute Lymphoblastic Leukemia
Kantarjian, H. M., Stein, A. S., Gökbuget, N., Fielding, A. K., Schuh, A. C., Ribera, J., Wei, A. H., Dombret, H., Foà, R., Bassan, R., et al. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1609783 · Cited by 2,204
STING-Dependent Cytosolic DNA Sensing Mediates Innate Immune Recognition of Immunogenic Tumors
Woo, S.-R., Fuertes, M. B., Corrales, L., Spranger, S., Furdyna, M. J., Leung, M. Y. K., Duggan, R., Wang, Y., Barber, G. N., Fitzgerald, K. A., et al. (2014) · Immunity · doi:10.1016/j.immuni.2014.10.017 · Cited by 1,917
Prodrugs: design and clinical applications
Rautio, J., Kumpulainen, H., Heimbach, T., Oliyai, R., Oh, D.-M., Järvinen, T., & Savolainen, J. (2008) · Nature Reviews Drug Discovery · doi:10.1038/nrd2468 · Cited by 1,681
Site-specific conjugation of a cytotoxic drug to an antibody improves the therapeutic index
Junutula, J. R., Raab, H. E., Clark, S., Bhakta, S., Leipold, D. D., Weir, S., Chen, Y., Simpson, M., Tsai, S. P., Dennis, M. S., et al. (2008) · Nature Biotechnology · doi:10.1038/nbt.1480 · Cited by 1,388
Anti-PD-1 and Anti-CTLA-4 Therapies in Cancer: Mechanisms of Action, Efficacy, and Limitations
Seidel, J. A., Otsuka, A., & Kabashima, K. (2018) · Frontiers in Oncology · doi:10.3389/fonc.2018.00086 · Cited by 1,360
Ogitani, Y., Aida, T., Hagihara, K., Yamaguchi, J., Ishii, C., Harada, N., Soma, M., Okamoto, H., Oitate, M., Arakawa, S., et al. (2016) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-15-2822 · Cited by 1,228
Unlocking the potential of antibody–drug conjugates for cancer therapy
Drago, J. Z., Modi, S., & Chandarlapaty, S. (2021) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-021-00470-8 · Cited by 1,209
Research works printed but not linked: 1
- CytomX Therapeutics Inc. CytomX therapeutics presents overview of conditionally-activated antibody-drug conjugate (ADC) programs including next generation EpCAM-targeting CX-2051. CytomX Press Release Details https://ir.cytomx.com/news-releases/news-release-details/cytomx-therapeutics-presents-overview-conditionally-activated/ (2022).
Cited by
Sorted by citations
Items 601–660 of 660
The Landscape of Clinical Trials for Antibody-Drug Conjugates in the Treatment of Ovarian CancerPreprint
chen, H., Chen, C., Zhang, Y., & Xu, L. (2026) · Research Square · doi:10.21203/rs.3.rs-10398827/v1
Biologic prodrugs: inactive protein and peptide drugs and drug conjugates with targeted activation
Oluoch, B., Marcotte, S., Miele, D., Cheng, J., Vogelaar, A., Si, J., & Zaro, J. L. (2026) · AAPS Open · doi:10.1186/s41120-026-00197-9
Conditionally active antibody‒drug conjugates
Guo, C., He, Y., Lu, Y., Dun, Q., Yang, J., & Wang, Y. (2026) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2026.08.023
Harkos, C., Munn, L. L., Stylianopoulos, T., & Jain, R. K. (2026) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2026-015357
Advances in Bispecific Antibodies and Antibody–Drug Conjugates for Colorectal Cancer Treatment
Cappellino, M. G., Sullivan, S. P., High, P. C., Blackburn, T. A., & Carmon, K. S. (2026) · Antibodies · doi:10.3390/antib15050080
Aqueous-Phase Peptide Synthesis via Stepwise Amino Acid Elongation Catalyzed by Aqualigase
Yan, X., Lin, Z., Chen, R., Huang, L., Tong, L., Gao, B., & Zhang, L. (2026) · ACS Organic & Inorganic Au · doi:10.1021/acsorginorgau.6c00067
Chorążewska, A., Ciura, K., Milczarek, M., Kłopotowska, D., Pomorski, A., Więch, A., Łukianowski, B., Gajdzis, P., Krężel, A., Bartoszewski, R., et al. (2026) · Journal of the American Chemical Society · doi:10.1021/jacs.6c08409
Antibody-Drug Conjugates in the Treatment of Esophageal Cancer
Wu, D., Chen, W., Zhao, Q., Zhu, W., & Xu, J. (2026) · Current Treatment Options in Oncology · doi:10.1007/s11864-026-01411-2
Molecular design and delivery of extracellular and membrane protein degradation chimeras
Lin, S., Zhou, H., Qiu, J., Dang, Y., Kou, L., Zhu, Z., Xu, Z., Lai, Y., & Yu, H. (2026) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2026.115959
Lou, J., & Lyu, Y. (2026) · Journal of Hematology & Oncology · doi:10.1186/s13045-026-01843-1
Zhang, J., Meng, Y., Du, Y., Sun, T., Cui, J., Chen, Y., Sun, Y., Wang, Y., Chen, W., Xu, F., et al. (2026) · Annals of Oncology · doi:10.1016/j.annonc.2026.09.002
Cai, W., Dai, S., Chen, Y., Cheng, C., & Chen, L. (2026) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2026.189712 · Cited by 1
Fu, Z., & Maynard, H. D. (2026) · Organic & Biomolecular Chemistry · doi:10.1039/d6ob01198e
From fixed antibody–drug conjugates to programmable therapeutics
Zhuang, X., & Pan, L. (2026) · Trends in cancer · doi:10.1016/j.trecan.2026.08.012
Neoadjuvant therapy in thyroid cancer: an emerging approach
Pitoia, F., Califano, I., Russell, M. D., Shonka, D. C., Trimboli, P., Fugazzola, L., & Randolph, G. W. (2026) · Endocrine · doi:10.1007/s12020-026-04797-z
Cai, H., Tao, T., Gao, Y., Tang, X., Chen, Y., & Zhang, H. (2026) · Cancers · doi:10.3390/cancers18183013
Advancements and future directions in transformative therapies of prostate cancer
Zhao, J., Tang, B., Zeng, H., & Wei, Q. (2026) · Chinese Medical Journal · doi:10.1097/cm9.0000000000004322
Safety management of anti TROP2 ADCs in patients with breast cancer
Malagutti, B., Malvezzi, G., & Zagami, P. (2026) · Current Opinion in Oncology · doi:10.1097/cco.0000000000001276
Li, Y., Li, Y., Huang, R., San, Z.-Q., & Ye, J. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1974912
Liu, H., Xu, L., Yang, S., Lin, J., Jin, D., Zeng, H., Qin, X., Yang, J., Xu, T., Wang, Y., et al. (2026) · Chemical Engineering Journal · doi:10.1016/j.cej.2026.182176
Zhang, Z., Yang, G., Liu, Y., Yu, Y., Zeng, X., Yin, C., Hong, X., & Zhou, H. (2026) · Chinese Chemical Letters · doi:10.1016/j.cclet.2026.113475
Site‐Specific Protein Bioconjugation Through Cellular Incorporation of Noncanonical Amino Acids
Sarkar, R., Joshi, M., & Chatterjee, A. (2026) · Angewandte Chemie International Edition · doi:10.1002/anie.1922738
Naei, V. Y., Dabiri, M., Chen, L., Li, J., Wang, I., Lin, G., & Warkiani, M. E. (2026) · Clinical and Translational Medicine · doi:10.1002/ctm2.70748
Jäger, S., Piater, B., Dickgießer, S., Tonillo, J., Hecht, S., Anderl, J., Minelli, F., Bertotti, E., Rasche, N., Joensuu, H., et al. (2026) · Bioconjugate Chemistry · doi:10.1021/acs.bioconjchem.6c00324
Site‐Specific Protein Bioconjugation Through Cellular Incorporation of Noncanonical Amino Acids
Sarkar, R., Joshi, M., & Chatterjee, A. (2026) · Angewandte Chemie · doi:10.1002/ange.1922738
Zhai, X., Xu, F., Su, P., Xie, Z., Liu, T., Zhou, T., Xu, M., Bao, B., & Wang, L. (2026) · Chemistry of Materials · doi:10.1021/acs.chemmater.6c01810
Antibody-drug conjugates in breast cancer: redefining targeted therapy
Guo, C., & Ellisen, L. W. (2026) · Journal of Clinical Investigation · doi:10.1172/jci207630
Feng, C., Wu, C., Heng, X., Wang, S., Yang, T., Li, X., Luo, D., Geng, J., & Huang, J. (2026) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2026.119387
Glycosylation in Quality and Safety of Therapeutic Proteins
Matsumoto, Y., Kim, J., McKenna, K. R., Biel, T. G., Kirshner, S., Falkowski, V. M., & Ju, T. (2026) · Pharmacological Reviews · doi:10.1016/j.pharmr.2026.100163
Micillo, M., Pirajno, B., Vallone, F. E., Navarro‐Tableros, V., Bolli, E., Griggio, V., Lannutti, B. J., Jessen, K., Vaisitti, T., & Deaglio, S. (2026) · HemaSphere · doi:10.1002/hem3.70478
Rathore, A. S., Guillarme, D., Beck, A., Peruri, V., & Dubey, S. (2026) · TrAC Trends in Analytical Chemistry · doi:10.1016/j.trac.2026.119179
Ianni, A. D., Molinaro, F., Barbero, L. M., Cowan, K. J., & Sirtori, F. R. (2026) · Journal of the American Society for Mass Spectrometry · doi:10.1021/jasms.6c00289
Exploring the immunological effects of antibody–drug conjugates
Zagami, P., Trapani, D., Marra, A., Carey, L., & Curigliano, G. (2026) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-026-01209-z
Wang, Z., Zhang, M., Li, Y., Jahromi, A. S., Liu, K., Zhao, J., & Li, G. (2026) · Biochemical Pharmacology · doi:10.1016/j.bcp.2026.118530
Tarantino, P., Valenza, C., Seguí, E., Lin, N., Prat, A., Curigliano, G., Waks, A. G., & Tolaney, S. M. (2026) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-026-01211-5
Zhao, L., An, S., Gao, M., Shen, C., Li, M., Li, Y., Liu, N., Chen, J., Wan, W., Yin, L., et al. (2026) · Cell Reports Medicine · doi:10.1016/j.xcrm.2026.103094
A modular framework for antibody–drug conjugate biomarkers
Liu, J., Ruan, D.-Y., McNamee, N., Reddel, R. R., Wu, H., Meng, Q., Xu, R., Subbiah, V., Rimm, D. L., & Pistilli, B. (2026) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-026-01213-3
Molecular and immune-mediated resistance to antibody-drug conjugates in breast cancer
Mattana, A., Veronese, C., Penitenti, J., Unti, E., Varotti, E., Vingiani, A., Lorenzini, D., Boffi, R., Graziosi, A., Danesi, R., et al. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1927515
NGS-guided discovery of cross-reactive TfR1 VHH antibodies with distinct brain localization profiles
Jatnika, M. F., Nagashima, A., Miyahara, W., Rafique, A., & Ito, Y. (2026) · The Journal of Biochemistry · doi:10.1093/jb/mvag070
Emerging Therapeutic targets and Early-phase drug Development in Gynecological Malignancies
Ouali, K., Tan, D., Lheureux, S., & Massard, C. (2026) · Annals of Oncology · doi:10.1016/j.annonc.2026.10.101
Sladkowski, M., & Wong, C. (2026) · Advances in computational intelligence and robotics book series · doi:10.4018/979-8-3373-6551-0.ch011
Chari, R. V. J., Shen, C., Clardy, S. M., Sévère, N., Meiser, N., Crochiere, M. L., & Balasubramanian, B. N. (2026) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.6c02354
Chemotherapy and targeted agents
Rosenstein, B. S., & Karp, J. M. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-13468-5.00006-0
Degradation-coupled antibody conjugates for precision cancer therapy
Zhuang, X., Lin, L., Zhang, Y., Wang, Y., & Pan, L. (2026) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2026.09.014
Caged Topoisomerase I Inhibitors for Green/Orange‐Light‐Activated Chemotherapy
Molnár, T. Á., Csorba, Z., Grád, A., Németh, K., & Bojtár, M. (2026) · ChemPhotoChem · doi:10.1002/cptc.70293
Alkunani, A. S., Shareef, L. G., & Arajy, A. Z. A. (2026) · Al-Rafidain Journal of Medical Sciences · doi:10.54133/ajms.v11i2.3258
Bioorthogonal chemistry conjugates: ADCs and beyond
Long, B., & Owen, S. C. (2026) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2026.115979
Bispecific antibodies in NSCLC: immune reengineering to neutralize adaptive tumor resistance
Li, Z., Wang, H., Diao, M., Liu, R., Wang, X., Xiong, A., Zhou, C., & Tang, Z. (2026) · Trends in cancer · doi:10.1016/j.trecan.2026.09.010
Cell-Based Assay Development and Standardization for Antibody–Drug Conjugates
Sun, D., Hsu, A. H.-M., Long, H., Qin, K., Welch, J., McCann, S., & Cheng, Z.-J. J. (2026) · BioTech · doi:10.3390/biotech15040096
Investigation of Antibody–Drug Conjugates by Mass Spectrometry
Arshad, A., Flack, R., Freire, I. B., Darie, C. C., & Jayathirtha, M. (2026) · Advances in experimental medicine and biology · doi:10.1007/978-3-032-29437-1_14
Kašpárková, J., Prachařová, J., & Brabec, V. (2026) · Inorganic Chemistry Frontiers · doi:10.1039/d6qi02172g
Wang, L., Feng, Y., Jia, R., & Liu, Q. (2026) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2026.105661
Yü, W., Wei, S., Wan, S., Chen, Y., & Huang, Q. (2026) · Frontiers in Pharmacology · doi:10.3389/fphar.2026.2001935
Matoba, Y., Rodman, E. P. B., Mohammadabadi, M. A., Bouberhan, S., Yeku, O., & Rueda, B. R. (2026) · Uterine Research · doi:10.1186/s44494-026-00006-w
Strategies for the intracellular synthesis of bioactive molecules in living cells
Cavadas, R. A. N., Bossons, N. D., Góis, P. M. P., & António, J. P. M. (2026) · Nature Reviews Chemistry · doi:10.1038/s41570-026-00888-7
Wan, K., & Liu, M. (2026) · Frontiers in Medicine · doi:10.3389/fmed.2026.1975216
Immune checkpoints: cross-disease insights and clinical dilemmas
Shu, Y., Zhao, J., Guo, B.-Y., Liu, Y., Zhou, M., Ma, N., Zhu, C.-L., & Zou, Z. (2026) · Biomarker Research · doi:10.1186/s40364-026-01030-x
Failla, M., Ubiali, E., Uggeri, F., Pecci, A., Marchini, M., Fiorito, D., Filocamo, G., Scheuermann, J., Pignataro, L., Steinkühler, C., et al. (2026) · Bioconjugate Chemistry · doi:10.1021/acs.bioconjchem.6c00445
Split Intein Enables Ultralarge Dual-Phage Display for Drug Discovery
Shi, L., Wang, W., Wang, D., Wang, Y., Chen, X., Wang, L.-J., Li, J., Fang, Z., Luo, J., Zhang, X., et al. (2026) · Journal of the American Chemical Society · doi:10.1021/jacs.6c11464
Metadata
- Authors
- Tsuchikama, K., Anami, Y., Ha, S. Y. Y., & Yamazaki, C. M.
- Affiliations
- Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases (US)
- Corresponding author
- Tsuchikama, Kyoji
- Venue
- Nature Reviews Clinical Oncology
- Published
- 2024-01-08
- Volume
- 21
- Issue
- 3
- Pages
- 203-223
- ISSN
- 1759-4774 (ISSN-L)
- 1759-4782
- OpenAlex
- W4390673654
- Cited by
- 659
- References
- 248
- Citations by year
- 2026: 282 · 2025: 270 · 2024: 106
- FWCI
- 42.66
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Nature Reviews Clinical Oncology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Defense (W81XWH1910598, W81XWH)
- National Institutes of Health (W81XWH)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Monoclonal and Polyclonal Antibodies Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Degradation and Inhibitors
- Life Sciences › Immunology and Microbiology › Immunology › Toxin Mechanisms and Immunotoxins
- Keywords
- antibody-drug conjugates, drug resistance, tumor heterogeneity, linker chemistry, chemical conjugation, payload design, patient stratification, biomarkers, treatment-refractory cancer, multimodal cancer therapy
- MeSH terms
- Antibodies, Monoclonal, Antineoplastic Agents, Pharmaceutical Preparations, Humans, Neoplasms, Immunoconjugates
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
