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    Redefining druggable targets with artificial intelligence
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    Redefining druggable targets with artificial intelligence

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    A vast landscape of ‘undruggable’ cancer targets remains beyond the reach of conventional therapeutic agents. Recent advances in artificial intelligence (AI), however, are challenging this paradigm. Synthesizing insights from a Cancer Moonshot workshop, we argue that systemically addressing the undruggable target space with AI requires a new conceptual framework. We highlight the failure of current target taxonomies and the need for benchmarking datasets, and re-evaluate clinical validation for novel AI-driven modalities.

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    Acknowledgements

    The workshop whose insights are summarized here was organized as part of the Cancer Moonshot initiative through joint efforts of the National Cancer Institute (NCI), Department of Energy (DOE), Advanced Research Projects Agency for Health (ARPA-H), and Food and Drug Administration (FDA). We thank the workshop organizing committee (J. Couch, S. Hanlon, A. Kilianski, J. Klemm, R. Philip and A. Predith) and all participants for their valuable contributions to the discussions and insights that shaped this Comment. Special thanks to the staff at the Hubert Humphrey Building for hosting the workshop and providing logistical support. This work was partially supported by the Cancer Moonshot initiative. The views expressed in this Comment are those of the authors and do not necessarily reflect the official policy or position of any government agency or institution.

    Author information

    Authors and Affiliations

    1. Schrödinger, New York, NY, USA

      Karen Akinsanya

    2. Department of Systems Biology, Columbia University, New York, NY, USA

      Mohammed AlQuraishi

    3. Dewpoint Therapeutics, Boston, MA, USA

      Ann Boija

    4. Memorial Sloan Kettering Cancer Center, New York, NY, USA

      John Chodera

    5. Harmonic Discovery, New York, NY, USA

      Anna Cichońska

    6. Massachusetts Institute of Technology, Cambridge, MA, USA

      Marzyeh Ghassemi & Regina Barzilay

    7. Amgen, Cambridge, MA, USA

      Martha Head

    8. Khoury College of Computer Science, Northeastern University, Boston, MA, USA

      Wengong Jin

    9. National Cancer Institute, Bethesda, MD, USA

      Warren A. Kibbe

    10. University of California San Francisco, San Francisco, CA, USA

      Nevan Krogan

    11. Genesis Therapeutics, Burlington, CA, USA

      Michael V. LeVine

    12. University of Maryland, College Park, MD, USA

      John Moult

    13. Institute for Protein Design, Seattle, WA, USA

      Lynda Stuart

    14. Oak Ridge National Laboratory, Oak Ridge, TN, USA

      Georgia Tourassi

    15. Stanford University, Stanford, CA, USA

      James Zou

    16. Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, USA

      Olivier Elemento

    Authors

    1. Karen Akinsanya
    2. Mohammed AlQuraishi
    3. Ann Boija
    4. John Chodera
    5. Anna Cichońska
    6. Marzyeh Ghassemi
    7. Martha Head
    8. Wengong Jin
    9. Warren A. Kibbe
    10. Nevan Krogan
    11. Michael V. LeVine
    12. John Moult
    13. Lynda Stuart
    14. Georgia Tourassi
    15. James Zou
    16. Regina Barzilay
    17. Olivier Elemento

    Contributions

    O.E. and R.B. co-chaired the workshop. All authors provided intellectual input via workshop discussions. O.E. drafted the manuscript. All authors reviewed, edited and approved the final manuscript.

    Corresponding authors

    Correspondence to
    Regina Barzilay or Olivier Elemento.

    Ethics declarations

    Competing interests

    A.B. is an employee and shareholder of Dewpoint Therapeutics and holds multiple patents related to the work discussed in this Comment. A.C. is an employee and stock option holder at Harmonic Discovery. K.A. is stock holder in Schrodinger and Nautilus Biotechnology. M.A. is a member of the scientific advisory boards of Cyrus Biotechnology, Deep Forest Sciences, Nabla Bio, Oracle Therapeutics, and Achira. O.E. is co-founder and stock holder in Volastra Therapeutics, holds stock in Freenome, serves as a member of the scientific advisory board (SAB) and holds stock options in Owkin, Harmonic Discovery, and Exai, is an SAB member for Canary Biosciences, and is receiving or has received funding from Eli Lilly, J&J/Janssen, Sanofi, AstraZeneca, and Volastra. J.C., M.G., M.H., W.J., W.A.K., N.K., M.V.L., J.M., L.S., G.T., J.Z., and R.B. declare no competing interests.

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    Cite this article

    Akinsanya, K., AlQuraishi, M., Boija, A. et al. Redefining druggable targets with artificial intelligence.
    Nat Biotechnol (2025). https://doi.org/10.1038/s41587-025-02770-1

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    • DOI: https://doi.org/10.1038/s41587-025-02770-1

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