Scappaticci F A, Marina N
Department of Pathology, Stanford University Medical Center, 269 Campus Drive, CCSR 3220, Stanford, CA 94305, USA.
Cancer Treat Rev. 2001 Dec;27(6):317-26. doi: 10.1053/ctrv.2001.0242.
The treatment of patients with soft tissue and bone sarcomas has dramatically improved over the last decade. This improvement has been brought about through advances in diagnosis, surgical techniques, conformal radiotherapy, and combination chemotherapy. Further advances in the management of the diverse spectrum of sarcoma patients will reflect tailoring of therapy based on molecular abnormalities. The role of cytogenetics and molecular analysis of fusion or mutated genes in diagnosis, prognosis, and design of biological treatments is discussed. An example of this approach has been the recent success in treatment of patients with gastrointestinal stromal tumours expressing mutant c-kit with a specific tyrosine kinase inhibitor, STI571. Molecular rearrangements may also serve as targets for designing specific immunotherapies with the fusion gene product. The use of biological therapies with signal transduction inhibitors, angiogenesis inhibitors, matrix metalloproteinase inhibitors, immunotherapy, differentiation inducers, and gene therapy could complement existing treatments for long-term control of disease. As these newer biological agents take form, clinical trial design will undergo change to reflect the chronic nature of these therapies.
在过去十年中，软组织和骨肉瘤患者的治疗有了显著改善。这种改善是通过诊断、手术技术、适形放疗和联合化疗的进步实现的。肉瘤患者多样化治疗管理的进一步进展将体现在基于分子异常的治疗方案定制上。本文讨论了细胞遗传学以及融合或突变基因的分子分析在诊断、预后和生物治疗设计中的作用。这种方法的一个例子是最近使用特异性酪氨酸激酶抑制剂STI571成功治疗了表达突变型c-kit的胃肠道间质瘤患者。分子重排也可能成为设计针对融合基因产物的特异性免疫疗法的靶点。使用信号转导抑制剂、血管生成抑制剂、基质金属蛋白酶抑制剂、免疫疗法、分化诱导剂和基因疗法等生物疗法可以补充现有治疗方法，以实现疾病的长期控制。随着这些新型生物制剂的形成，临床试验设计将发生变化，以反映这些疗法的慢性性质。
