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Peer-reviewedCC BYCancer Cell

Antibody-drug conjugates in precision oncology

  • Barbara Pistilli1
  • Raffaele Colombo2
  • Maria Fernanda Mosele3
  • Sarat Chandarlapaty4
4 affiliations
  1. 1Department of Medical Oncology, Gustave Roussy, Villejuif, France; IHU PRISM National PRecISion Medicine Center in Oncology, Gustave Roussy, Villejuif, France. Electronic address: [email protected]
  2. 2ADC Therapeutic Development, Zymeworks Inc., Vancouver, BC, Canada
  3. 3IHU PRISM National PRecISion Medicine Center in Oncology, Gustave Roussy, Villejuif, France; INSERM U981, Gustave Roussy, Paris, France; Drug Development Department (DITEP), Gustave Roussy, Villejuif, France
  4. 4Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Weill Cornell Medical College, New York, NY, USA
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Abstract

Antibody-drug conjugates (ADCs) represent a growing therapeutic class in oncology marked by several transformative clinical successes. However, these exceptional outcomes remain restricted to a limited number of tumor types, and ADC development has been marked by frequent clinical setbacks, underscoring persistent challenges in optimal patient selection, biomarker assay standardization, chemical design, and the limited predictive value of existing preclinical models. Despite broader advances in precision oncology, ADC development has largely occurred without validated biomarkers. Emerging evidence indicates that ADC activity extends beyond target antigen expression alone, encompassing tumor-intrinsic features and tumor microenvironment-dependent processes. This challenges the view of ADCs as strictly targeted agents and supports their conceptualization as tumor-ecosystem-targeting therapies governed by multidimensional biological determinants. In this review, we link ADC successes and setbacks to mechanisms of efficacy, resistance, and toxicity, and discuss how biomarkers, ADC combinations, next-generation platforms, and curative-intent strategies should shape precision oncology frameworks.

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Cite

BibTeXRIS
BibTeX
@article{pistilli2026antibodydrug,
  title = {{Antibody-drug conjugates in precision oncology}},
  author = {Barbara Pistilli and Raffaele Colombo and Maria Fernanda Mosele and Sarat Chandarlapaty},
  journal = {Cancer Cell},
  year = {2026},
  month = jun,
  doi = {10.1016/j.ccell.2026.05.004},
  url = {https://doi.org/10.1016/j.ccell.2026.05.004},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Antibody-drug conjugates in precision oncology
AU  - Barbara Pistilli
AU  - Raffaele Colombo
AU  - Maria Fernanda Mosele
AU  - Sarat Chandarlapaty
PY  - 2026
DA  - 2026/06/01
JO  - Cancer Cell
DO  - 10.1016/j.ccell.2026.05.004
UR  - https://doi.org/10.1016/j.ccell.2026.05.004
AB  - Antibody-drug conjugates (ADCs) represent a growing therapeutic class in oncology marked by several transformative clinical successes. However, these exceptional outcomes remain restricted to a limited number of tumor types, and ADC development has been marked by frequent clinical setbacks, underscoring persistent challenges in optimal patient selection, biomarker assay standardization, chemical design, and the limited predictive value of existing preclinical models. Despite broader advances in precision oncology, ADC development has largely occurred without validated biomarkers. Emerging evidence indicates that ADC activity extends beyond target antigen expression alone, encompassing tumor-intrinsic features and tumor microenvironment-dependent processes. This challenges the view of ADCs as strictly targeted agents and supports their conceptualization as tumor-ecosystem-targeting therapies governed by multidimensional biological determinants. In this review, we link ADC successes and setbacks to mechanisms of efficacy, resistance, and toxicity, and discuss how biomarkers, ADC combinations, next-generation platforms, and curative-intent strategies should shape precision oncology frameworks.
SN  - 1535-6108
SN  - 1878-3686
ER  -