Stein Eytan, Aranha Olivia, Agulnik Mark
Department of Medicine, Northwestern University, Feinberg School of Medicine, Chicago, IL 60611, USA.
Oncology (Williston Park). 2008 Feb;22(2):206-11; discussion 215-6, 219.
Gastrointestinal stromal tumors have until recently had a uniformly poor prognosis with lack of effective drug therapies. These tumors usually have activating mutations in either KIT or PDGFR-alpha tyrosine kinase receptors. Over the past decade, imatinib (Gleevec), a selective tyrosine kinase inhibitor has become the standard of care for the first-line treatment of patients with unresectable and metastatic disease. For patients with imatinib-resistant disease or intolerant to the side effects of imatinib, sunitinib (Sutent), a multitargeted tyrosine kinase inhibitor was recently approved. For earlier-stage disease, status post-complete surgical excision, preliminary data seem encouraging for the role of adjuvant imatinib in prolonging patients' disease-free interval. The impact of neoadjuvant drug therapy needs to be further classified and explored. With additional evaluation of other tyrosine kinase inhibitors and novel therapies against other molecular markers, the treatment paradigm for this malignancy should continue to evolve.
直到最近,胃肠道间质瘤的预后一直普遍较差,且缺乏有效的药物治疗方法。这些肿瘤通常在KIT或血小板衍生生长因子受体α(PDGFR-α)酪氨酸激酶受体中存在激活突变。在过去十年中,伊马替尼(格列卫),一种选择性酪氨酸激酶抑制剂,已成为不可切除和转移性疾病患者一线治疗的标准疗法。对于对伊马替尼耐药或不耐受其副作用的患者,一种多靶点酪氨酸激酶抑制剂舒尼替尼(索坦)最近获得批准。对于早期疾病,在完全手术切除后,辅助性伊马替尼在延长患者无病间期方面的作用,初步数据似乎令人鼓舞。新辅助药物治疗的影响需要进一步分类和探索。随着对其他酪氨酸激酶抑制剂和针对其他分子标志物的新型疗法的进一步评估,这种恶性肿瘤的治疗模式应会持续演变。