title: Beyond imatinib: second generation c-KIT inhibitors for the management of gastrointestinal stromal tumors.
abstract: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal cancer of teh gastrointestinal tract. They are characterized by the expression of KIT. Therapeutically, metastatic GISTs are effectively treated by imatinib, a tyrosine kinase inhibitor (TKI) with activity against KIT and platelet-derived growth factor receptor. Gastrointestinal stromal tumors refractory to standard therapy with imatinib are a clinical challenge. This has lead to the clinical testing of a variety of agents used alone or in combination with other TKIs. Sunitinib, a multitargeted TKI, is the first drug available fort eh treatment of these patients. Additional trials are ongoing, evaluating the efficacy of the novel KIT TKIs AMG 706 and AMN 107 (nilotinib). RAD001, PKC412, and bavacizumab are being tested in conjunction with imatinib. Lastly, the heat-shock protein-90 inhibitor IPI-540 is also in phase I evaluation in imatinib-refractory patients with GIST. The future management of GIST is likely to be altered by the availability of more agents and by better biologic understanding of the patient populations each agent best treats.
authors.affiliation: Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA. margaret.vonmehren@fccc.edu
authors.forename: Margaret
authors.initials: M
authors.lastname: von Mehren
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D000068258:Bevacizumab; D002986:Clinical Trials as Topic; D000069439:Dasatinib; D019008:Drug Resistance, Neoplasm; D000068338:Everolimus; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy*; D006801:Humans; D000068877:Imatinib Mesylate; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007211:Indoles / Q000627:therapeutic use*; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D009841:Oligonucleotides; D010879:Piperazines / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D019009:Proto-Oncogene Proteins c-kit / Q000187:drug effects*; D011743:Pyrimidines / Q000627:therapeutic use; D011758:Pyrroles / Q000627:therapeutic use; D020123:Sirolimus / Q000031:analogs & derivatives / Q000627:therapeutic use; D019311:Staurosporine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000077210:Sunitinib; D013844:Thiazoles / Q000627:therapeutic use
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D001549:Benzamides; D007166:Immunosuppressive Agents; D007211:Indoles; D009841:Oligonucleotides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011758:Pyrroles; D013844:Thiazoles; D009536:Niacinamide; D000068258:Bevacizumab; D000068877:Imatinib Mesylate; D000068338:Everolimus; D019009:Proto-Oncogene Proteins c-kit; C498826:nilotinib; C519562:imetelstat; D019311:Staurosporine; C059539:midostaurin; D000069439:Dasatinib; D000077210:Sunitinib; D020123:Sirolimus