Targeted therapy for gastrointestinal stromal tumors: current status and future perspectives.
Gastrointestinal stromal tumors (GISTs) present 80% of gastrointestinal tract mesenchymal tumors, with systemic chemotherapy and radiotherapy being unable to improve survival of patients with advanced disease. The identification of activating mutations in either KIT cell surface growth factor receptor or platelet-derived growth factor receptor alpha, which lead to ligand-independent signal transduction, paved the way for the development of novel agents that selectively inhibit key molecular events in disease pathogenesis. The development of imatinib mesylate in the treatment of metastatic GIST represents a therapeutic breakthrough in molecularly targeted strategies, which crucially improved patients' prognosis while its usefulness in adjuvant and neoadjuvant setting is under study. Sunitinib malate is available in the second-line setting, with ongoing studies evaluating its role in an earlier disease stage, while other targets are under intense investigation in order to enrich the therapeutical armamentarium for this disease. GIST phenotype seems to be an essential indicator of treatment response; thus, obtaining genotype information of each patient may be critical in order to tailor individualized treatment strategies and achieve maximal therapeutic results.
Papaetis
Georgios S
GS
Oncology Unit, 3rd Department of Medicine, Athens School of Medicine, Sotiria General Hospital, Athens, Greece. gpapaetis@yahoo.gr
Syrigos
Kostas N
KN
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001549:Benzamides; D002986:Clinical Trials as Topic / Q000379:methods; D016503:Drug Delivery Systems / Q000379:methods*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics; D046152:Gastrointestinal Stromal Tumors / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D000068877:Imatinib Mesylate; D008495:Medical Oncology / Q000639:trends; D010879:Piperazines / Q000627:therapeutic use; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011743:Pyrimidines / Q000627:therapeutic use
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate