C-kit, GIST, and imatinib.
A gain-of-function mutation of c-kit is the crucial step in tumorigenesis of gastrointestinal stromal tumors (GIST). Imatinib can block the activated receptor tyrosine kinase activity of c-kit. These findings made GIST an ideal candidate for evaluation of new targeted therapeutic approaches. Clinical studies demonstrated that, with imatinib, objective responses can be reached in more than 50% of patients with advanced GIST. Furthermore, even in those patients with stable disease, long-term tumor control could be achieved. Therefore imatinib at a dose of 400 mg/day is now the standard treatment of advanced GIST in which RO-resection cannot be reached. As imatinib resistance in GIST occurs at a median of 18 to 26 months, further targeted therapies have been explored. Sunitinib, another tyrosine kinase inhibitor, seems to be useful especially in patients with exon 9 mutations of c-kit, who usually have a worse response to imatinib. This might indicate that more exactly targeted therapies in GIST might improve clinical outcomes in the future.
Siehl
Jan
J
Medizinische Klinik III (Hematology, Oncology and Transfusion Medicine), Charité Campus Benjamin Franklin, Berlin, Germany.
Thiel
Eckhard
E
D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001549:Benzamides; D019008:Drug Resistance, Neoplasm; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D000068877:Imatinib Mesylate; D007211:Indoles / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D019009:Proto-Oncogene Proteins c-kit / Q000187:drug effects* / Q000235:genetics; D011743:Pyrimidines / Q000494:pharmacology / Q000627:therapeutic use*; D011758:Pyrroles / Q000627:therapeutic use; D000077210:Sunitinib
D000970:Antineoplastic Agents; D001549:Benzamides; D007211:Indoles; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011758:Pyrroles; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit; D000077210:Sunitinib