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Attacking cancer at its foundation

Nature Medicine volume 15, pages 1153–1157 (2009)Cite this article

Foundational discoveries connecting the fields of viral oncogenes and human protein kinases stimulated a number of groups to begin drug discovery programs targeting these kinases. The clinical success of some of these programs has created much interest in protein kinase inhibitors in almost all pharmaceutical companies. Looking back on the development of imatinib, it would be easy to view its evolution as a relatively straightforward task. However, for those working in the protein kinase inhibitor field in the 1980s, the challenges were not insignificant. A strong basic scientific foundation, combined with a productive collaboration between industry and academia, and a mixture of skill, luck and perseverance was required to deliver imatinib from the laboratory to the clinic.

The foundation on which imatinib discovery was built

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Figure 1: Diagram of the translocation that creates the Philadelphia chromosome.
Figure 2: Status of the protein kinase family in the mid-1980s, when the kinase program at Ciba-Geigy began.
Figure 3: Lead optimization.
Figure 4: Imatinib bound to the inactive, closed confirmation of ABL.
Figure 5: Kinase dendrogram interaction maps for imatinib, dasatinib and sunitinib.
Figure 6: Characterization and annotation of compound libraries.

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Acknowledgements

I am grateful to the many people who have participated in the imatanib project, including my former laboratory staff and research and development colleagues at Ciba-Geigy (Novartis), and the many clinical scientists involved in the imatinib clinical program. I would like to acknowledge the major contributions made by E. Buchdunger, B. Druker, H. Mett, P. Traxler and J. Zimmermann. I would also like to acknowledge the support and mentoring of A. Matter and G. Haas during my time at Ciba-Geigy and T. Roberts and B. Hemmings for their support and scientific advice. I would like to thank P. Zarrinker for providing Figures 5 and 6.

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  1. Nicholas Lydon is at Grant Biopharma, Jackson, Wyoming, USA.,

    Nicholas Lydon

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Correspondence to Nicholas Lydon.

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Competing interests

N.L. is a Science Advisory Board member for Ambit Biosciences, and he is an owner of stock in Ambit.

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Lydon, N. Attacking cancer at its foundation. Nat Med 15, 1153–1157 (2009). https://doi.org/10.1038/nm1009-1153

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