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COSMIC-3D provides structural perspectives on cancer genetics for drug discovery

Nature Genetics volume 50, pages 1200–1202 (2018)Cite this article

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To the Editor – COSMIC-3D is a comprehensive integration of cancer mutations with protein structure across the human genome and structural proteome, seeking to support the identification and characterization of protein targets for novel drug design in precision oncology. As an interactive system to explore cancer mutations in 3D, COSMIC-3D is designed to enable greater understanding of the functional impact of mutations, generate new hypotheses on which mutations are cancer drivers and provide new opportunities for addressing these mutations pharmaceutically. This combination of genetics, structural proteomics and drug development can be best described as ‘mutation-guided drug design’.

There is a substantial need in precision oncology for treatments directed at specific cancer-associated mutations, to more effectively treat patient populations with specific genomic profiles. Recently, huge gains in targeted and genomic DNA sequencing are driving a growing knowledge of which mutations cause cancer. Yet, relative to these gains in genomic knowledge, there remains much scope for expansion of the repertoire of precision therapeutic drugs targeting these mutations. Concurrently, the number of publicly available protein structures has been growing exponentially. Both cancer genomic and protein structural data sources are individually great assets for scientists working in the field of oncology drug discovery. However, linking these two important resources enables a much greater understanding of the protein structural aspects of cancer, empowering targeted drug design across cancer-associated proteins.

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Fig. 1: Individual views of mutation, mutation frequency and protein sequence in COSMIC-3D.

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Acknowledgements

We thank colleagues at the Wellcome Sanger Institute and Astex Pharmaceuticals for helpful comments. This work was funded by a postdoctoral fellowship awarded to H.C.J. under the Sustaining Innovation Postdoctoral Training Program at Astex Pharmaceuticals (H.C.J., H.K.S., M.L.V., S.A.F.). This work was supported by a Wellcome Trust grant (206194) (H.C.J., S.A.F.).

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Authors and Affiliations

  1. COSMIC, Wellcome Sanger Institute, Cambridge, UK

    Harry C. Jubb & Simon A. Forbes

  2. Astex Pharmaceuticals, Cambridge, UK

    Harry C. Jubb, Harpreet K. Saini & Marcel L. Verdonk

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  1. Harry C. Jubb
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  2. Harpreet K. Saini
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  3. Marcel L. Verdonk
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  4. Simon A. Forbes
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Contributions

H.C.J. contributed experimental design, performed the experiments, analyzed the data and wrote the manuscript. H.K.S., M.L.V. and S.A.F. contributed joint supervision of research, conception and design of the experiments, and writing of the manuscript.

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Correspondence to Harry C. Jubb.

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Competing interests

COSMIC-3D uses data and systems infrastructure from the COSMIC database group, which is partly funded from Wellcome Trust charitable funds together with sales of licenses to for-profit enterprises. H.K.S. and M.L.V. are employed by Astex Pharmaceuticals.

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Jubb, H.C., Saini, H.K., Verdonk, M.L. et al. COSMIC-3D provides structural perspectives on cancer genetics for drug discovery. Nat Genet 50, 1200–1202 (2018). https://doi.org/10.1038/s41588-018-0214-9

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