When the tyrosine kinase inhibitor imatinib (Gleevec) was found to induce high remission rates in patients with chronic myeloid leukemia, this was hailed as a success for targeted tumor therapy. Since then, the repertoire of cancer types that respond to such inhibitors has expanded and researchers are beginning to grapple with the problem of acquired drug resistance. The activating kinase mutations targeted by these drugs can be viewed as the Achilles heel of cancer—they promote malignant progression, yet can turn cancer into a therapeutically exploitable disease.
This is a preview of subscription content, log in via an institution to check access.
References
Hunter, T. & Eckhart, W. Cell 116, S35–S39, 1 p following S48 (2004).
Gschwind, A., Fischer, O.M. & Ullrich, A. Nat. Rev. Cancer 4, 361–370 (2004).
Manning, G., Whyte, D.B., Martinez, R., Hunter, T. & Sudarsanam, S. Science 298, 1912–1934 (2002).
Rowley, J.D. Nature 243, 290–293 (1973).
Heisterkamp, N. et al. Nature 344, 251–253 (1990).
Kelliher, M.A., McLaughlin, J., Witte, O.N. & Rosenberg, N. Proc. Natl. Acad. Sci. USA 87, 6649–6653 (1990).
Daley, G.Q., Van Etten, R.A. & Baltimore, D. Science 247, 824–830 (1990).
Noble, M.E., Endicott, J.A. & Johnson, L.N. Science 303, 1800–1805 (2004).
Buchdunger, E. et al. Cancer Res. 56, 100–104 (1996).
Druker, B.J. et al. Nat. Med. 2, 561–566 (1996).
Druker, B.J. et al. N. Engl. J. Med. 344, 1031–1037 (2001).
Druker, B.J. et al. N. Engl. J. Med. 344, 1038–1042 (2001).
O'Brien, S.G. et al. N. Engl. J. Med. 348, 994–1004 (2003).
Buchdunger, E. et al. J. Pharmacol. Exp. Ther. 295, 139–145 (2000).
Buchdunger, E. et al. Proc. Natl. Acad. Sci. USA 92, 2558–2562 (1995).
Joensuu, H. et al. N. Engl. J. Med. 344, 1052–1056 (2001).
Heinrich, M.C. et al. J. Clin. Oncol. 21, 4342–4349 (2003).
Apperley, J.F. et al. N. Engl. J. Med. 347, 481–487 (2002).
Cools, J. et al. N. Engl. J. Med. 348, 1201–1214 (2003).
Rubin, B.P. et al. J. Clin. Oncol. 20, 3586–3591 (2002).
Gorre, M.E. et al. Science 293, 876–880 (2001).
Azam, M., Latek, R.R. & Daley, G.Q. Cell 112, 831–843 (2003).
Shah, N.P., Tran, C., Lee, F.Y., Chen, P., Norris, D. & Sawyers, C.L. Science 305, 399–401 (2004).
Demetri, G.D. et al. Proc. Am. Soc. Clin. Oncol. 23, 195 (2004).
Mendelsohn, J. & Baselga, J. J. Clin. Oncol. 21, 2787–2799 (2003).
Kaelin, W.G. Jr. Sci. STKE 2004, pe12 (2004).
Arteaga, C.L. & Baselga, J. Cancer Cell 5, 525–531 (2004).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Baselga, J., Arribas, J. Treating cancer's kinase 'addiction'. Nat Med 10, 786–787 (2004). https://doi.org/10.1038/nm0804-786
Issue Date:
DOI: https://doi.org/10.1038/nm0804-786
- Springer Nature America, Inc.
This article is cited by
-
Pristimerin induces apoptosis in imatinib-resistant chronic myelogenous leukemia cells harboring T315I mutation by blocking NF-κB signaling and depleting Bcr-Abl
Molecular Cancer (2010)
-
Carcinogenesis, cancer therapy and chemoprevention
Cell Death & Differentiation (2005)