Magenau John M, Schuetze Scott M
Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
Curr Opin Oncol. 2008 Jul;20(4):400-6. doi: 10.1097/CCO.0b013e328303671d.
Systemic treatment options for advanced sarcoma remain limited. Emerging trends exploring targeted therapy for the treatment of sarcoma are reviewed here.
Effective treatments for metastatic sarcoma after the failure of front line regimens, such as doxorubicin, ifosfamide, and gemcitabine with docetaxel, are clearly limited. Translational research has identified a significant proportion of sarcomas with characteristic molecular changes potentially amenable to targeted therapy. Aberrant signaling of mammalian target of rapamycin and tyrosine kinase pathways have been focal points of recent research. Early trials investigating biologic inhibitors of these pathways have yielded varied clinical results. Agents targeting stem cell factor receptor (C-KIT), platelet-derived growth factor receptor, mammalian target of rapamycin, and vascular endothelial growth factor receptor have all shown efficacy to some degree in advanced sarcoma. The insulinlike growth factor-1 receptor is a potentially important target for sarcoma treatment based on early clinical results.
Sarcomas are a heterogeneous group of tumors and targeted agents likely have a long-term role in their treatment. Identifying critical pathways in sarcomagenesis, susceptible subtypes and developing novel combinations remain the focus of future research.
晚期肉瘤的全身治疗选择仍然有限。本文综述了探索肉瘤靶向治疗的新趋势。
一线治疗方案(如多柔比星、异环磷酰胺以及吉西他滨联合多西他赛)失败后,转移性肉瘤的有效治疗方法明显有限。转化研究已确定相当一部分肉瘤具有可能适合靶向治疗的特征性分子变化。雷帕霉素哺乳动物靶点和酪氨酸激酶途径的异常信号传导一直是近期研究的重点。针对这些途径的生物抑制剂的早期试验产生了不同的临床结果。靶向干细胞因子受体(C-KIT)、血小板衍生生长因子受体、雷帕霉素哺乳动物靶点和血管内皮生长因子受体的药物在晚期肉瘤中均已显示出一定程度的疗效。基于早期临床结果,胰岛素样生长因子-1受体是肉瘤治疗的一个潜在重要靶点。
肉瘤是一组异质性肿瘤,靶向药物可能在其治疗中发挥长期作用。确定肉瘤发生中的关键途径、易感亚型并开发新的联合治疗方案仍是未来研究的重点。