The GIST of targeted cancer therapy: a tumor (gastrointestinal stromal tumor), a mutated gene (c-kit), and a molecular inhibitor (STI571).
Although gastrointestinal stromal tumor (GIST) is the most frequent mesenchymal neoplasm of the gastrointestinal tract, until recently it has been an obscure disease. Now, there is widespread scientific and clinical interest in GIST because its principal pathogenetic defect has been identified and a specific molecular inhibitor of GIST has been developed. Most GISTs contain a gain-of-function mutation in the c-kit proto-oncogene. Mutation results in constitutive activation of the Kit receptor tyrosine kinase, which induces cellular proliferation. STI571 is an oral agent that selectively inhibits Kit. It is a landmark development in cancer treatment and marks a new era of targeted molecular therapy. Its efficacy proves that a specific inhibitor can counteract the effects of a genetic defect responsible for neoplasia. Although STI571 was first applied to GIST only 2 years ago, it has already revolutionized the treatment of patients with metastatic disease and is also currently being tested as an adjuvant therapy after the resection of primary GIST.
DeMatteo
Ronald P
RP
Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA. dematter@mskcc.org
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D004621:Embolization, Therapeutic; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000601:surgery / Q000628:therapy*; D006499:Hepatic Artery; D006801:Humans; D000068877:Imatinib Mesylate; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000556:secondary; D009154:Mutation; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D000090063:Proto-Oncogene Mas; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D011743:Pyrimidines / Q000494:pharmacology / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D001549:Benzamides; D004791:Enzyme Inhibitors; C000715470:MAS1 protein, human; D010879:Piperazines; D000090063:Proto-Oncogene Mas; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; D019009:Proto-Oncogene Proteins c-kit