A review of resistance patterns and phenotypic changes in gastrointestinal stromal tumors following imatinib mesylate therapy.
Gastrointestinal stromal tumors are neoplastic lesions that arise from the interstitial cells of Cajal and are associated with somatic mutations in the tyrosine kinase receptor, KIT. The only known curative therapy is complete surgical resection. Unfortunately, postsurgical recurrence rates exceed 50% and most tumors are resistant to standard chemotherapy and radiation. Imatinib mesylate, a novel tyrosine kinase inhibitor, holds promise as a potential adjuvant therapy to prevent recurrence and improve long-term survival. However, as resistance data emerge, it appears that a potential "escape pathway" may originate from secondary mutations in the KIT receptor. This paper reviews the historical clinical experience with imatinib mesylate and discusses resistance patterns following targeted therapy. We highlight this review with an interesting case report that illustrates unique phenotypic tumoral changes associated with imatinib mesylate resistance.
Bickenbach
Kai
K
Department of Surgery, University of Chicago Pritzker School of Medicine, 5841 S. Maryland Avenue, Chicago, IL 60637, USA.
Wilcox
Rebecca
R
Veerapong
Jula
J
Kindler
Hedy Lee
HL
Posner
Mitchell C
MC
Noffsinger
Amy
A
Roggin
Kevin King
KK
D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005743:Gastrectomy; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D006801:Humans; D000068877:Imatinib Mesylate; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000601:surgery / Q000628:therapy; D010641:Phenotype; D010879:Piperazines / Q000627:therapeutic use*; D019009:Proto-Oncogene Proteins c-kit / Q000502:physiology; D011743:Pyrimidines / Q000627:therapeutic use*; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000235:genetics*
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit