Soft tissue sarcomas of adults: state of the translational science.
Soft tissue sarcomas of adults: state of the translational science.
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发表时间：
2003-06
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通讯作者：
E. Borden;L. Baker;R. Bell;V. Bramwell;G. Demetri;B. Eisenberg;C. Fletcher;J. Fletcher;M. Ladanyi;P. Meltzer;B. O'Sullivan;D. Parkinson;P. Pisters;S. Saxman;S. Singer;M. Sundaram;A. V. van Oosterom;J. Verweij;J. Waalen;S. Weiss;M. Brennan
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作者：
E. Borden;L. Baker;R. Bell;V. Bramwell;G. Demetri;B. Eisenberg;C. Fletcher;J. Fletcher;M. Ladanyi;P. Meltzer;B. O'Sullivan;D. Parkinson;P. Pisters;S. Saxman;S. Singer;M. Sundaram;A. V. van Oosterom;J. Verweij;J. Waalen;S. Weiss;M. Brennan
肉瘤与白血病一样，也是中胚层恶性肿瘤，其生物学意义与其临床频率不成比例。与这些肿瘤相关的突变和易位的鉴定阐明了导致这些疾病的异常信号传导途径，决定了它们的行为，并且是治疗靶标。 Activated receptor-associated tyrosine kinase c-kit, mutated in most gastrointestinal stromal tumors, has proven a clinically effective target for enzyme inhibition.已在五种不同的肉瘤中发现了涉及由 EWS 和相关基因组成的单个基因家族的易位，并且其嵌合蛋白产物可能同样适合抑制剂。分子和染色体特征数据有助于解决组织病理学的复杂性。影像学、预后因素的定义以及手术和放射治疗的改进改善了局部控制。持续的进展将取决于进一步适应快速发展的基因组学和蛋白质组学技术。它还将取决于准确的组织病理学诊断，该诊断基于经过验证的试剂和应用于来自具有完整临床数据的患者的足够组织样本的一致方法。最后，多中心协调试验，例如评估甲磺酸伊马替尼治疗转移性胃肠道间质瘤的试验，将确保最快速地降低发病率和死亡率。
Sarcomas--like leukemias, which are also mesodermal malignancies--carry biological significance disproportionate to their clinical frequency. Identification of mutations and translocations associated with these tumors has illuminated aberrant signaling pathways that cause these diseases, determine their behavior, and are therapeutic targets. Activated receptor-associated tyrosine kinase c-kit, mutated in most gastrointestinal stromal tumors, has proven a clinically effective target for enzyme inhibition. A translocation involving a single gene family, consisting of EWS and related genes, has been identified in five different sarcomas, and its chimeric protein products could prove similarly amenable to inhibitors. Resolution of the histopathological complexity is being aided by data from molecular and chromosomal characterization. Improvements in imaging, definition of prognostic factors, and surgical and radiotherapeutic treatment have resulted in improved local control. Continued progress will depend on further adapting the rapidly evolving technologies of genomics and proteomics. It will also depend upon accurate histopathological diagnosis based on validated reagents and consistent methodologies applied to adequate tissue samples derived from patients with complete clinical data. Finally, multicenter, coordinated trials, such as those that occurred with assessment of imatinib mesylate in metastatic gastrointestinal stromal tumors, will assure the most rapid reductions in morbidity and mortality.