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Hépato-Gastro & Oncologie Digestive

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Clinical management of advanced gastrointestinal stromal tumors Volume 25, issue 9, Novembre 2018

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Institut Bergonié, Département de Médecine, 229 cours de l’Argonne, 33076 Bordeaux Cedex, France
* Tirés à part

Approximately 90% of gastrointestinal tumors (GISTs) harbor an activating mutation in KIT or PDGFRα oncogene known to confer imatinib sensitivity. Imatinib is a tyrosine kinase inhibitor of KIT and PDGFRs that yields a 6-months progression-free survival (PFS) rate of 80% in patients with advanced GISTs. Several studies have shown that response to imatinib in GIST patients mainly depends on the mutational status of KIT or PDGFRα. Moreover, most if not all patients treated with imatinib for advanced GIST will secondarily develop progressive disease under treatment. In the majority of cases, such progressions are the result of acquired resistance due to occurrence of secondary C-KIT mutations; especially for GIST with primary exon 11 mutations. Sunitinib and regorafenib are inhibitors of multiple tyrosine kinases including C-KIT, PDGFRα as well as PDGFRβ and VEGFRs and approved for the management of imatinib- and imatinib/sunitinib-refractory GIST patients respectively. Clearly, a better knowledge of the molecular mechanisms underlying the resistance to imatinib as well as the development of a new class of broad-spectrum tyrosine kinase inhibitors may allow in the near future new individualized therapeutic strategies for GISTs patients.

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