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References
Kuhn, T.S. The Structure of Scientific Revolutions. (University of Chicago Press, Chicago, 1962).
Goldman, J.M. et al. Ann. Intern. Med. 108, 806–814 (1988).
Nowell, P.C. & Hungerford, D.A. J. Natl. Cancer Inst. 25, 85–109 (1960).
Rowley, J.D. Nature 243, 290–293 (1973).
de Klein, A. et al. Nature 300, 765–767 (1982).
Shtivelman, E., Lifshitz, B., Gale, R.P. & Canaani, E. Nature 315, 550–554 (1985).
Konopka, J.B., Watanabe, S.M., Singer, J.W., Collins, S.J. & Witte, O.N. Proc. Natl. Acad. Sci. USA 82, 1810–1814 (1985).
Mes-Masson, A.M., McLaughlin, J., Daley, G.Q., Paskind, M. & Witte, O.N. Proc. Natl. Acad. Sci. USA 83, 9768–9772 (1986).
Daley, G.Q., Van Etten, R.A. & Baltimore, D. Science 247, 824–830 (1990).
Druker, B.J. et al. Nat. Med. 2, 561–566 (1996).
Weinstein, I.B. Science 297, 63–64 (2002).
Gorre, M.E. et al. Science 293, 876–880 (2001).
Shah, N.P. et al. Cancer Cell 2, 117–125 (2002).
Shah, N.P. et al. Science 305, 399–401 (2004).
Talpaz, M. et al. N. Engl. J. Med. 354, 2531–2541 (2006).
Shah, N.P. et al. J. Clin. Invest. 117, 2562–2569 (2007).
Acknowledgements
Without the discovery of imatinib by N. Lydon and the demonstration of its preclinical activity by B. Druker, none of the work described here would have been possible. I am forever grateful to Brian and Nick for inviting me to join them on this project. I am indebted to O. Witte for accepting me into his laboratory when I was a naive oncology fellow and training me to think like a scientist. There could be no better mentor for an aspiring physician-scientist. I thank M. Talpaz for teaching me the intricacies of CML and for a wonderful partnership in the clinical development of imatinib and dasatinib. I am especially grateful for the hard work and dedication of the many graduate students, postdoctoral trainees and technicians who have been a part of my group over the past 16 years—you are my second family. I especially want to single out M. Gorre and N. Shah, who broke the resistance story and worked essentially 24-7 for much of 2001–2002 to be sure we had it right and to follow up on the implications for next-generation inhibitors. It is hard to envision a more invigorating time in the laboratory, where the results of each experiment made a difference. The insights that led us to dasatinib would never have been possible without J. Kuriyan, who showed me the power of structural biology (with a front-row seat and three-dimensional glasses at his lab group meetings). I still owe John a beer for the figure he made in 2001 showing steric hindrance caused by the T315I mutation, but I suspect my obligation has now grown to a case of champagne. The dasatinib story emerged from a wonderful collaboration on the preclinical work with F. Lee and R. Kramer at Bristol-Myers Squibb, then on the clinical development with A. DeCillis, C. Nicaise and R. Canetta. One of the unique aspects of life as a physician-scientist is the opportunity to care for patients who, in effect, are the laboratory for your translational ideas. I had the privilege to care for several hundred patients with CML from 1998 to 2006, all of whom volunteered their lives to allow us to test our hypotheses. Many patients from the very early trials are no longer with us, but many others still are. I thank all of them and their families for their courage and inspiration. The clinical trials of imatinib and dasatinib were conducted in record time, requiring an amazing team of individuals working together to handle the volume of patients and clinical data collected. I especially want to thank my UCLA colleagues R. Paquette, L. Haddad, G. Naessig, D. Slamon and J. Gasson for all their support during the two-year period from 2000 to 2001 that none of us will ever forget. Lastly, I thank my family for all their support, encouragement and understanding. My parents, John and Julia Sawyers, both physicians, have been my role models from the beginning. My children, Sophie and Sam, amaze me every day with their sense of adventure and curiosity about everything in life. My wife, Susan, has been my companion and confidant for the past 21 years. She keeps me on an even keel and smiling all day long.
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Sawyers, C. Shifting paradigms: the seeds of oncogene addiction. Nat Med 15, 1158–1161 (2009). https://doi.org/10.1038/nm1009-1158
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DOI: https://doi.org/10.1038/nm1009-1158
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