This Article Full Text Full Text (PDF) eLetters: Submit a response to this article Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services E-mail this article link to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints/Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sleijfer, S. Articles by Verweij, J. Search for Related Content PubMed PubMed Citation Articles by Sleijfer, S. Articles by Verweij, J.

Sarcomas

Improved Insight into Resistance Mechanisms to Imatinib in Gastrointestinal Stromal Tumors: A Basis for Novel Approaches and Individualization of Treatment

Department of Medical Oncology, Erasmus University Medical Centre, Daniel den Hoed Cancer Centre, Rotterdam, The Netherlands

Key Words. GIST • Imatinib • Resistance • Sunitinib

Correspondence: Stefan Sleijfer, M.D., Ph.D. Department of Medical Oncology, Erasmus University Medical Centre, Daniel den Hoed Cancer Centre, Groene Hilledijk 301, 3075 EA Rotterdam, The Netherlands. Telephone: 31-010-4391733; Fax: 31-010-4391003; e-mail: s.sleijfer{at}erasmusmc.nl

Gastrointestinal stromal tumor (GIST) is one of the first solid tumor types in which a tyrosine kinase inhibitor, imatinib, has become standard of care for patients with advanced disease. Although imatinib yields antitumor activity in the vast majority of patients, it is likely that all patients eventually experience progressive disease given enough time. In recent years, major progress has been made in the elucidation of mechanisms conferring resistance to imatinib that result in progressive disease. Insight into these resistance mechanisms has already resulted in the availability of strategies that can be applied in cases of progressive disease and it is likely that more approaches will be defined in the next years. Additionally, it can be anticipated that in the near future treatment will be guided according to factors determining sensitivity to imatinib. This review focuses on the factors inducing imatinib resistance that have been elucidated so far, the currently available and potential novel treatment options for patients with progressive disease, and how insight into resistance mechanisms may allow individualized treatment in the near future for patients with advanced GISTs.

Disclosure of potential conflicts of interest is found at the end of this article.

This article has been cited by other articles:

				G. Floris, M. Debiec-Rychter, R. Sciot, C. Stefan, S. Fieuws, K. Machiels, P. Atadja, A. Wozniak, G. Faa, and P. Schoffski High Efficacy of Panobinostat Towards Human Gastrointestinal Stromal Tumors in a Xenograft Mouse Model Clin. Cancer Res., June 15, 2009; 15(12): 4066 - 4076. [Abstract] [Full Text] [PDF]

				C. A. London, P. B. Malpas, S. L. Wood-Follis, J. F. Boucher, A. W. Rusk, M. P. Rosenberg, C. J. Henry, K. L. Mitchener, M. K. Klein, J. G. Hintermeister, et al. Multi-center, Placebo-controlled, Double-blind, Randomized Study of Oral Toceranib Phosphate (SU11654), a Receptor Tyrosine Kinase Inhibitor, for the Treatment of Dogs with Recurrent (Either Local or Distant) Mast Cell Tumor Following Surgical Excision Clin. Cancer Res., June 1, 2009; 15(11): 3856 - 3865. [Abstract] [Full Text] [PDF]

				J. S. Lagas, R. A.B. van Waterschoot, V. A.C.J. van Tilburg, M. J. Hillebrand, N. Lankheet, H. Rosing, J. H. Beijnen, and A. H. Schinkel Brain Accumulation of Dasatinib Is Restricted by P-Glycoprotein (ABCB1) and Breast Cancer Resistance Protein (ABCG2) and Can Be Enhanced by Elacridar Treatment Clin. Cancer Res., April 1, 2009; 15(7): 2344 - 2351. [Abstract] [Full Text] [PDF]