title: Inactivity of imatinib in gastrointestinal stromal tumors (GISTs) harboring a KIT activation-loop domain mutation (exon 17 mutation pN822K).
abstract: The development of gastrointestinal stromal tumors (GISTs) is largely driven by mutations in the KIT and PDGFRα genes. Imatinib mesylate is an oral small molecular tyrosine kinase inhibitor that mainly targets abl, c-KIT, and PDGFRα. Imatinib achieves disease control in approximately 70%-85% of patients with advanced GIST, and the median progression-free survival is 20-24 months. The efficacy of imatinib correlates with tumor kinase mutational status (exon 11 mutations mainly), and some mutations are known to be responsible for primary and secondary imatinib resistance. Beyond these, there are many other mutations that are considered rare and are associated with unknown clinical behavior. In the literature, there are poor and inconsistent data about the inhibitor sensitivity of mutations occurring in the activation-loop domain encoded by exon 17. In this article, we focus on a case of a patient suffering from GIST, harboring an extremely rare KIT activation-loop domain mutation (exon 17 mutation pN822K) treated with imatinib. A review of the literature is also presented.
authors: Division of Chest Medical Oncology, Rare Tumors and Sarcomas, European Institute of Oncology, Milan, Italy.
authors: Gianluca
authors: G
authors: Spitaleri
authors: Division of Abdominal Surgery, Rare Tumors and Sarcomas, European Institute of Oncology, Milan, Italy.
authors: Roberto
authors: R
authors: Biffi
authors: Division of Pathology, Rare Tumors and Sarcomas, European Institute of Oncology, Milan, Italy.
authors: Massimo
authors: M
authors: Barberis
authors: Division of Pathology, Rare Tumors and Sarcomas, European Institute of Oncology, Milan, Italy.
authors: Caterina
authors: C
authors: Fumagalli
authors: Division of Chest Medical Oncology, Rare Tumors and Sarcomas, European Institute of Oncology, Milan, Italy.
authors: Francesca
authors: F
authors: Toffalorio
authors: Division of Chest Medical Oncology, Rare Tumors and Sarcomas, European Institute of Oncology, Milan, Italy.
authors: Chiara
authors: C
authors: Catania
authors: Division of Chest Medical Oncology, Rare Tumors and Sarcomas, European Institute of Oncology, Milan, Italy.
authors: Cristina
authors: C
authors: Noberasco
authors: Division of Chest Medical Oncology, Rare Tumors and Sarcomas, European Institute of Oncology, Milan, Italy.
authors: Chiara
authors: C
authors: Lazzari
authors: Division of Chest Medical Oncology, Rare Tumors and Sarcomas, European Institute of Oncology, Milan, Italy.
authors: Filippo
authors: F
authors: de Marinis
authors: Oncology Unit of Thymic cancer, Rare Tumors and Sarcomas, European Institute of Oncology, Milan, Italy.
authors: Tommaso
authors: T
authors: De Pas
keywords: GIST; KIT activation-loop domain mutation; drug resistance; imatinib