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  • Perspective
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Past, present and future of drug conjugates for cancer therapy

Nature Cancer volume 6, pages 1494–1504 (2025)Cite this article

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Abstract

Drug conjugates have emerged as promising tumor-targeted cytotoxics with an improved therapeutic index compared to classical chemotherapeutics. Although traditionally based on antibody ligands, high-throughput screening methods, such as peptide display and DNA-encoded chemical libraries, have enabled the isolation of ultra-high-affinity small ligands and the generation of drug conjugates with better tumor-targeting performance. This Perspective examines the history, major clinical milestones and future of drug conjugates for cancer treatment. We also discuss a new wave of combination modalities, linker strategies, and the development of conjugates based on large and small delivery vehicles.

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Fig. 1: A schematic comparison between conventional chemotherapy and tumor-targeted moieties.
Fig. 2: Mechanism of action of ADCs.
Fig. 3: History of approvals of targeted cytotoxics.
Fig. 4: From large antibody-based drug conjugates to PDCs and SMDCs.

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Acknowledgements

We thank G. Rotta for the support in preparing the original figures. The preparation of this article was entirely funded by Philochem AG.

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  1. These authors contributed equally: S. Cazzamalli, E. Puca.

Authors and Affiliations

  1. R&D Department, Philochem AG, Otelfingen, Switzerland

    S. Cazzamalli & E. Puca

  2. Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology, Zurich, Switzerland

    D. Neri

  3. Philogen S.p.A., Siena, Italy

    D. Neri

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  1. S. Cazzamalli
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  2. E. Puca
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Correspondence to D. Neri.

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D.N. is the cofounder, CEO, CSO and President of the Scientific Advisory Board of Philogen. S.C. and E.P. are employed by Philochem AG, the research and development unit of the Philogen Group.

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Cazzamalli, S., Puca, E. & Neri, D. Past, present and future of drug conjugates for cancer therapy. Nat Cancer 6, 1494–1504 (2025). https://doi.org/10.1038/s43018-025-01042-w

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