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  • Review Article
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Drug Insight: gastrointestinal stromal tumors (GIST)—the solid tumor model for cancer-specific treatment

Nature Clinical Practice Oncology volume 5, pages 102–111 (2008)Cite this article

Abstract

We are living in an exciting era in the treatment of cancer, using drugs that target specific proteins rather than agents that cause more general cytotoxic effects. The identification of proteins and signal transduction pathways that play crucial roles in the pathogenesis of cancer has allowed treatments to be designed that target these tumor-driven events. Gastrointestinal stromal tumors (GIST) are rare mesenchymal tumors and were among the first solid tumor types for which such a novel treatment (in this case imatinib) became available. The tyrosine kinase inhibitor imatinib targets the human KIT receptor and the platelet-derived growth factor receptor-α. This drug exhibits impressive antitumor effects against GIST and has become the first-line therapy for advanced disease. Major insights into the mechanism of action of this drug, drug resistance, and patient management issues have been gleaned. Additionally, new drugs developed for the treatment of GIST have been identified. As a consequence, lessons learned from GIST are widely applicable to other tumor entities, thereby rendering GIST the paradigm of solid tumors treated with tyrosine kinase inhibitors. This Review discusses the pathogenesis of GIST, treatment strategies, mechanisms accounting for drug resistance, and potential future perspectives.

Key Points

  • Improved insights into the molecular mechanisms that cause malignancy have been the foundation of the development of “cancer-(cell-)specific therapy” with tyrosine kinase inhibitors for the treatment of gastrointestinal stromal tumors (GIST)

  • Understanding the mechanisms that confer resistance against tyrosine kinase inhibitors has yielded additional novel treatment strategies for GIST

  • Elucidation of prognostic and predictive factors in GIST offers opportunities for individualizing patient treatment

  • GIST has become the paradigm for the treatment of solid tumors with tyrosine kinase inhibitors

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Figure 1: Imatinib-induced cystic alterations in hepatic metastases from a patient with GIST.

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Acknowledgements

This research was supported by the EC FP6 CONTICANET project (LSHC-CT-2005-018806) from the European Commission.

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Authors and Affiliations

  1. and J Verweij is Professor of Medical Oncology with tenure in the Department of Medical Oncology, S Sleijfer is a Staff Member, E Wiemer is a Staff Member and Research Group Leader, Erasmus University Medical Centre, Rotterdam, The Netherlands.,

    Stefan Sleijfer, Erik Wiemer & Jaap Verweij

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Correspondence to Stefan Sleijfer.

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Sleijfer, S., Wiemer, E. & Verweij, J. Drug Insight: gastrointestinal stromal tumors (GIST)—the solid tumor model for cancer-specific treatment. Nat Rev Clin Oncol 5, 102–111 (2008). https://doi.org/10.1038/ncponc1037

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