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Current and Emerging Pharmacological Treatments for Gastrointestinal Stromal Tumour

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Abstract

Gastrointestinal stromal tumours (GIST) are the most common mesenchymal tumours of the gastrointestinal tract, previously classified as leiomyosarcomas. Most GIST express KIT and the majority have mutations in the KIT gene. The most common KIT mutation occurs in the juxtamembrane domain of exon 11. These mutations lead to cellular proliferation and survival. GIST with exon 11 mutations respond better to tyrosine kinase inhibitors (TKIs) than those with exon 9 mutations. Most KIT-negative GIST express platelet-derived growth factor receptor (PDGFR)-α; however, a small percentage of GIST are negative for both KIT and PDGFRα. Imatinib and other TKIs have dramatically improved the outcome of patients with metastatic GIST. Newer and more advanced TKIs are under intense investigation as eventually all GIST patients develop resistant tumours. In addition, these drugs can be utilized in the pre-operative setting for patients with unresectable localized tumours or those at high risk for surgical morbidity. TKIs have been given in the adjuvant setting for patients with resected tumours at high risk for recurrence. The duration of adjuvant therapy is currently under evaluation; however, it is possible that these patients would need to continue therapy indefinitely.

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Acknowledgements

No sources of funding were used to assist in the preparation of this review. Dr Patel has received honoraria from Novartis for speaking and advising. Dr Ganjoo has no conflicts of interest that are directly relevant to the content of this review.

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Authors and Affiliations

  1. Department of Medicine, Division of Oncology, Stanford Comprehensive Cancer Center, Stanford, California, USA

    Kristen N. Ganjoo

  2. Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Sarcoma Center, Houston, Texas, USA

    Shreyaskumar Patel

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Correspondence to Kristen N. Ganjoo.

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Ganjoo, K.N., Patel, S. Current and Emerging Pharmacological Treatments for Gastrointestinal Stromal Tumour. Drugs 71, 321–330 (2011). https://doi.org/10.2165/11585370-000000000-00000

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