Novel approaches to gastrointestinal stromal tumors resistant to imatinib and sunitinib.
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.
Cassier
Philippe A
PA
Conticanet Network of Excellence (LSH-060188), Département de Medicine, Centre Léon Bérard, 28 Rue Laennec, 69008 Lyon, France.
Dufresne
Armelle
A
Arifi
Samia
S
El Sayadi
Hiba
H
Ray-Coquard
Isabelle
I
Bringuier
Pierre-Paul
PP
Scoazec
Jean-Yves
JY
Alberti
Laurent
L
Blay
Jean-Yves
JY
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
D000970:Antineoplastic Agents; D001549:Benzamides; D007211:Indoles; D010879:Piperazines; D011743:Pyrimidines; D011758:Pyrroles; D000068877:Imatinib Mesylate; D000077210:Sunitinib