Treatment of gastrointestinal stromal tumors with imatinib mesylate: a major breakthrough in the understanding of tumor-specific molecular characteristics.
A specific treatment for gastrointestinal stromal tumors (GIST) has been found through improved understanding of the molecular mechanism of carcinogenesis. GIST are radio and chemo-resistant (less than 10 objective responses). Stromal tumors originate from the multiplication of the cells of Cajal, which intervene in intestinal motility and express the c-Kit gene, also called CD117, on their surface. CD117 is a protein with tyrosine kinase activity, and can be demonstrated through immunohistochemical staining techniques. Treatment with Imatinib mesylate (Glivec), a recently discovered selective inhibitor of tyrosine kinases already used in chronic myeloid leukemia (in which an overexpression of tyrosine kinase is observed) was associated with tumor regression of more than 50% in the initial series of patients with GIST treated in 2001. Since then, approximately 2,000 patients have been included in therapeutic trials, with an objective response rate between 60% and 70% 12 to 18 months after inclusion. The clinical benefit has been estimated at 80% to 90% in patients whose chance of survival until now has been less than 30% at one year (median survival 18 months). Nonetheless, imatinib mesylate has not shown any activity in CD117-negative sarcoma (10% of sarcoma). The therapeutic importance of this drug in the treatment of solid GI tumors deemed inoperable is considerable.
de Mestier
Philippe
P
Unite de Chirurgie Generale et Digestive, Hopital des Peupliers, 8 place de I'abbe G. Henocque, 75013, Paris, France. ph.demestier@attglobal.net
des Guetz
Gaetan
G
D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001549:Benzamides; D046152:Gastrointestinal Stromal Tumors / Q000175:diagnosis / Q000188:drug therapy* / Q000601:surgery; D006801:Humans; D000068877:Imatinib Mesylate; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate