{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T13:59:15Z","timestamp":1790690355814,"version":"4.1.0"},"reference-count":36,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,2,14]],"date-time":"2025-02-14T00:00:00Z","timestamp":1739491200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI19\/00808"],"award-info":[{"award-number":["PI19\/00808"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["000\/2023"],"award-info":[{"award-number":["000\/2023"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["000\/2024"],"award-info":[{"award-number":["000\/2024"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["AOF.C01CRIS"],"award-info":[{"award-number":["AOF.C01CRIS"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"name":"ACEPAIN","award":["PI19\/00808"],"award-info":[{"award-number":["PI19\/00808"]}]},{"name":"ACEPAIN","award":["000\/2023"],"award-info":[{"award-number":["000\/2023"]}]},{"name":"ACEPAIN","award":["000\/2024"],"award-info":[{"award-number":["000\/2024"]}]},{"name":"ACEPAIN","award":["AOF.C01CRIS"],"award-info":[{"award-number":["AOF.C01CRIS"]}]},{"name":"CRIS Cancer Foundation","award":["PI19\/00808"],"award-info":[{"award-number":["PI19\/00808"]}]},{"name":"CRIS Cancer Foundation","award":["000\/2023"],"award-info":[{"award-number":["000\/2023"]}]},{"name":"CRIS Cancer Foundation","award":["000\/2024"],"award-info":[{"award-number":["000\/2024"]}]},{"name":"CRIS Cancer Foundation","award":["AOF.C01CRIS"],"award-info":[{"award-number":["AOF.C01CRIS"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background: Antibody\u2013drug conjugates (ADCs) represent a novel therapeutic class that combines an antibody against a tumor-associated antigen (TAA), a payload, and a linker that binds these two components. Serious adverse events (SAEs), particularly those of grade 3 (G3) or higher, frequently contribute to the abandonment of ADCs during clinical development. Methods: In this study, we analyzed the toxicity profiles of all approved ADCs, aiming to uncover correlations between their safety profiles and the specific characteristics of their components. Results: In our analysis, dose reductions, dose delays, treatment discontinuations, and \u2265G3 toxicities were not significantly different across payload types. Similarly, no association was found between the payload mechanism of action and \u2265G3 toxicities, including anemia, neutropenia, febrile neutropenia, thrombocytopenia, and diarrhea. By exploring the specific toxicities of ADCs observed by organ, we identified that most were related to the payload mechanism of action, like the \u2265G3 diarrhea observed in 10% of patients treated with sacituzumab govitecan (the payload SN-38 is the active metabolite of irinotecan), and very few were related to the presence of the TAA in normal tissue (presence of Nectin-4 in skin and \u2265G3 rash toxicity in 14% of patients treated with enfortumab vedotin). In line with this, no major differences in \u2265G3 toxicities were identified in studies with different levels of the TAA (trastuzumab deruxtecan in Destiny Breast Studies with different HER2 expression levels). Conclusions: Our analysis reveals that most ADC toxicities are driven by the payload\u2019s effects on non-transformed tissues; however, a detailed analysis of each ADC component should be taken into consideration.<\/jats:p>","DOI":"10.3390\/pharmaceutics17020258","type":"journal-article","created":{"date-parts":[[2025,2,14]],"date-time":"2025-02-14T11:14:41Z","timestamp":1739531681000},"page":"258","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Understanding the Toxicity Profile of Approved ADCs"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-7200-0155","authenticated-orcid":false,"given":"Pablo","family":"Ballest\u00edn","sequence":"first","affiliation":[{"name":"Experimental Therapeutics Unit, Departamento Oncolog\u00eda M\u00e9dica, Instituto de Investigaci\u00f3n Sanitaria San Carlos (IdISSC), Hospital Cl\u00ednico San Carlos (HCSC), 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfonso","family":"L\u00f3pez de S\u00e1","sequence":"additional","affiliation":[{"name":"Experimental Therapeutics Unit, Departamento Oncolog\u00eda M\u00e9dica, Instituto de Investigaci\u00f3n Sanitaria San Carlos (IdISSC), Hospital Cl\u00ednico San Carlos (HCSC), 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"D\u00edaz-Tejeiro","sequence":"additional","affiliation":[{"name":"Experimental Therapeutics Unit, Departamento Oncolog\u00eda M\u00e9dica, Instituto de Investigaci\u00f3n Sanitaria San Carlos (IdISSC), Hospital Cl\u00ednico San Carlos (HCSC), 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc\u00eda","family":"Paniagua-Herranz","sequence":"additional","affiliation":[{"name":"Experimental Therapeutics Unit, Departamento Oncolog\u00eda M\u00e9dica, Instituto de Investigaci\u00f3n Sanitaria San Carlos (IdISSC), Hospital Cl\u00ednico San Carlos (HCSC), 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6511-2498","authenticated-orcid":false,"given":"Adri\u00e1n","family":"Sanvicente","sequence":"additional","affiliation":[{"name":"Experimental Therapeutics Unit, Departamento Oncolog\u00eda M\u00e9dica, Instituto de Investigaci\u00f3n Sanitaria San Carlos (IdISSC), Hospital Cl\u00ednico San Carlos (HCSC), 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor","family":"L\u00f3pez-Cade","sequence":"additional","affiliation":[{"name":"Experimental Therapeutics Unit, Departamento Oncolog\u00eda M\u00e9dica, Instituto de Investigaci\u00f3n Sanitaria San Carlos (IdISSC), Hospital Cl\u00ednico San Carlos (HCSC), 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro","family":"P\u00e9rez-Segura","sequence":"additional","affiliation":[{"name":"Experimental Therapeutics Unit, Departamento Oncolog\u00eda M\u00e9dica, Instituto de Investigaci\u00f3n Sanitaria San Carlos (IdISSC), Hospital Cl\u00ednico San Carlos (HCSC), 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7588-0781","authenticated-orcid":false,"given":"Carlos","family":"Alonso-Moreno","sequence":"additional","affiliation":[{"name":"Unidad nanoDrug, Centro de Innovaci\u00f3n en Qu\u00edmica Avanzada (ORFEO-CINQA), Departamento de Qu\u00edmica Inorg\u00e1nica, Org\u00e1nica y Bioqu\u00edmica, Facultad de Farmacia, Universidad de Castilla-La Mancha, 02071 Albacete, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3463-1439","authenticated-orcid":false,"given":"Cristina","family":"Nieto-Jim\u00e9nez","sequence":"additional","affiliation":[{"name":"Experimental Therapeutics Unit, Departamento Oncolog\u00eda M\u00e9dica, Instituto de Investigaci\u00f3n Sanitaria San Carlos (IdISSC), Hospital Cl\u00ednico San Carlos (HCSC), 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1067-9630","authenticated-orcid":false,"given":"Alberto","family":"Oca\u00f1a","sequence":"additional","affiliation":[{"name":"Experimental Therapeutics Unit, Departamento Oncolog\u00eda M\u00e9dica, Instituto de Investigaci\u00f3n Sanitaria San Carlos (IdISSC), Hospital Cl\u00ednico San Carlos (HCSC), 28040 Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Oncolog\u00eda (CIBERONC), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1038\/nrclinonc.2010.194","article-title":"Preclinical development of molecular-targeted agents for cancer","volume":"8","author":"Ocana","year":"2010","journal-title":"Nat. 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