Advances in the treatment of gastrointestinal stromal tumor.
GIST (gastrointestinal stromal tumor) is a rare soft tissue malignancy arising in the gut. It has become well known recently because of the effectiveness of anti-KIT tyrosine kinase inhibitors. From a disease that 10 years ago was only treatable with surgery, now multiple phase 2 and phase 3 trials have identified active first-line systemic therapy, appropriate dosing, an active second-line agent, and established the role of adjuvant therapy after surgery for patients with intermediate- and high-risk tumors. These are accomplishments that took decades to achieve for other more common diseases such as breast cancer or lung cancer. GIST has been the ideal disease system for studying targeted therapy in solid tumors. The progress in treating GIST has come directly from the advances that have been made in the laboratory, understanding the basic biology of tyrosine kinases, the oncogenic activity of c-KIT, and how that enzymatic activity can be inhibited. By studying model diseases such as GIST, we should be able to develop paradigms to treat more common cancers as well.
D'Adamo
David
D
Memorial Sloan Kettering Cancer Center, New York, NY, USA. dadamod@mskcc.org
D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001549:Benzamides; D003131:Combined Modality Therapy; D016503:Drug Delivery Systems; D019008:Drug Resistance, Neoplasm; D015507:Drugs, Investigational; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D006801:Humans; D000068877:Imatinib Mesylate; D007211:Indoles / Q000009:adverse effects / Q000627:therapeutic use; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D019009:Proto-Oncogene Proteins c-kit / Q000037:antagonists & inhibitors*; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use; D011758:Pyrroles / Q000009:adverse effects / Q000627:therapeutic use; D000077210:Sunitinib
D000970:Antineoplastic Agents; D001549:Benzamides; D015507:Drugs, Investigational; D007211:Indoles; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011758:Pyrroles; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit; D000077210:Sunitinib