title: Novel approaches to gastrointestinal stromal tumors resistant to imatinib and sunitinib.
abstract: Gastrointestinal stromal tumors (GIST) are rare tumors of mesenchymal origin that may arise anywhere along the gastrointestinal tract or in the peritoneum. In most cases, GIST harbor mutations of KIT or PDGFRA. Imatinib mesylate (IM), a small-molecule tyrosine kinase inhibitor developed for the treatment of chronic myeloid leukemia, has been shown to be active against these mutations and has significant activity in patients with metastatic GIST. However, resistance to IM emerges after a median of 24 months of treatment. Sunitinib malate (SU) has been approved for the treatment of patients with IM-resistant advanced GIST, but the median progression-free survival in this setting is only 6 months. This article reviews the current knowledge regarding IM and SU resistance in GIST, as well as the available options for the management of GIST resistant to IM and SU.
authors.affiliation: Conticanet Network of Excellence (LSH-060188), Département de Medicine, Centre Léon Bérard, 28 Rue Laennec, 69008 Lyon, France.
authors.forename: Philippe A
authors.initials: PA
authors.lastname: Cassier
authors.forename: Armelle
authors.initials: A
authors.lastname: Dufresne
authors.forename: Samia
authors.initials: S
authors.lastname: Arifi
authors.forename: Hiba
authors.initials: H
authors.lastname: El Sayadi
authors.forename: Isabelle
authors.initials: I
authors.lastname: Ray-Coquard
authors.forename: Pierre-Paul
authors.initials: PP
authors.lastname: Bringuier
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Scoazec
authors.forename: Laurent
authors.initials: L
authors.lastname: Alberti
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Blay
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D001549:Benzamides; D003131:Combined Modality Therapy; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D046152:Gastrointestinal Stromal Tumors / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D006801:Humans; D000068877:Imatinib Mesylate; D007211:Indoles / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D000077210:Sunitinib
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D007211:Indoles; D010879:Piperazines; D011743:Pyrimidines; D011758:Pyrroles; D000068877:Imatinib Mesylate; D000077210:Sunitinib