Acquired resistance to imatinib in gastrointestinal stromal tumours caused by multiple KIT mutations

In summary, imatinib treatment of gastrointestinal stromal tumours might lead to secondary resistance because of newly acquired KIT mutations affecting different synchronous codons and exons in different tumour manifestations of the same patient. More studies on the heterogeneity of acquired KIT mutations are needed to improve understanding of the biology of metastatic lesions of gastrointestinal stromal tumours during imatinib treatment. Our results might affect the development of alternate therapeutic strategies in patients with progressive gastrointestinal stromal tumours. Strategies might include surgical resection of single, progressive lesions as well as introduction of new moleculartargeted substances such as SU11248, another multitargeted tyrosine kinase-inhibitor that might overcome imatinib resistance.