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.
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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.
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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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Akinsanya, K., AlQuraishi, M., Boija, A. et al. Redefining druggable targets with artificial intelligence. Nat Biotechnol 43, 1416–1418 (2025). https://doi.org/10.1038/s41587-025-02770-1
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DOI: https://doi.org/10.1038/s41587-025-02770-1
