von Mehren Margaret
Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA.
Clin Colorectal Cancer. 2006 Nov;6 Suppl 1:S30-4. doi: 10.3816/ccc.2006.s.005.
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.
胃肠道间质瘤（GISTs）是胃肠道最常见的间叶性肿瘤。它们的特征是KIT蛋白表达。在治疗方面，转移性GISTs可通过伊马替尼有效治疗，伊马替尼是一种酪氨酸激酶抑制剂（TKI），对KIT和血小板衍生生长因子受体具有活性。对伊马替尼标准治疗难治的胃肠道间质瘤是一项临床挑战。这导致了多种单独使用或与其他TKI联合使用的药物的临床试验。舒尼替尼，一种多靶点TKI，是第一种可用于治疗这些患者的药物。其他试验正在进行中，评估新型KIT TKI AMG 706和AMN 107（尼洛替尼）的疗效。RAD001、PKC412和贝伐单抗正在与伊马替尼联合进行测试。最后，热休克蛋白-90抑制剂IPI-540也正在对伊马替尼难治的GIST患者进行I期评估。随着更多药物的出现以及对每种药物最适合治疗的患者群体有更好的生物学理解，GIST的未来管理可能会发生改变。
