Twenty Years on: What Do We Really Know about Ewing Sarcoma and What Is the Path Forward?
Twenty Years on: What Do We Really Know about Ewing Sarcoma and What Is the Path Forward?
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DOI：
10.1615/critrevoncog.2015013553
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发表时间：
2015
影响因子：
--
通讯作者：
Sorensen PH
中科院分区：
文献类型：
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作者：
Lawlor ER;Sorensen PH
尤文肉瘤（ES）是一种高度侵袭性的骨和软组织肿瘤，在青少年和年轻人中发病率最高。尽管在局部控制和全身化疗方面取得了进展，但初始临床缓解后的转移性复发仍然是一个重要的临床问题。此外，在出现或复发时的转移仍然是诊断为ES的患者的主要死亡原因。自从20多年前特异性EWS-FLI 1融合基因的发现以来，人们对ES发病机制的分子和细胞生物学已经有了很多了解。此外，最近开发的干细胞和发育生物学的进展提供了关键的见解ES的细胞起源和肿瘤的起始和维持中的表观遗传失调的作用。然而，驱动肿瘤复发和转移的机制在很大程度上仍然未知。我们知识上的这些差距继续阻碍着新的治疗策略的发展，这些策略将改善复发性和转移性疾病患者的结局。在本章中，我们将回顾ES生物学研究的现状，突出我们提出的最有潜力产生将转化为临床重大进展的发现的调查领域。
Ewing sarcoma (ES) is a highly aggressive bone and soft tissue tumor with peak incidence in adolescents and young adults. Despite advances in local control and systemic chemotherapy, metastatic relapse after an initial clinical remission remains a significant clinical problem. In addition, metastasis at the time of presentation or at relapse continues to be the leading cause of death for patients diagnosed with ES. Since the discovery over 20 years ago of the pathognomonic EWS-FLI1 fusion gene, much has been learned about the molecular and cellular biology of ES pathogenesis. In addition, more recent exploitation of advances in stem cell and developmental biology has provided key insights into the cellular origins of ES and the role of epigenetic deregulation in tumor initiation and maintenance. Nevertheless, the mechanisms that drive tumor relapse and metastasis remain largely unknown. These gaps in our knowledge continue to hamper the development of novel therapeutic strategies that will improve outcomes for patients with relapsed and metastatic disease. In this chapter we will review the current status of ES biology research, highlighting areas of investigation that we propose have the greatest potential to yield findings that will translate into clinically significant advances.