Exploiting Replication Stress as a Novel Therapeutic Intervention.
Exploiting Replication Stress as a Novel Therapeutic Intervention.
复制标题
利用复制应力作为一种新型的治疗干预措施。
DOI：
10.1158/1541-7786.mcr-20-0651
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发表时间：
2021-03
期刊：
影响因子：
--
通讯作者：
Ohm JE
中科院分区：
文献类型：
--
作者：
Martin JC;Hoegel TJ;Lynch ML;Woloszynska A;Melendy T;Ohm JE
尤文肉瘤是一种侵袭性的小儿骨和软组织肿瘤。目前的标准治疗是放疗和化疗，患者通常缺乏靶向治疗。这种肿瘤类型的定义分子特征之一是与正常细胞和许多其他类型的癌症相比，存在显著升高的复制应激水平，但这种应激的来源知之甚少。具有高水平复制应激的肿瘤依赖于复制应激和DNA损伤反应途径来保持活力。了解尤文肉瘤中复制应激的来源可能会揭示新的治疗靶点。尤文肉瘤的发生是复杂的，在这篇综述中，我们讨论了目前的状态，我们的知识提高复制应力和DNA损伤反应尤文肉瘤，疾病过程的贡献者之一。我们还将描述这些途径是如何在其他肿瘤类型中成功靶向治疗的，并讨论尤文肉瘤中可能的新的循证治疗干预措施。我们希望这一整合将引发发现新的治疗靶点的研究，并为尤文肉瘤患者提供更好的治疗选择。
Ewing sarcoma is an aggressive pediatric tumor of the bone and soft tissue. The current standard of care is radiation and chemotherapy, and patients generally lack targeted therapies. One of the defining molecular features of this tumor type is the presence of significantly elevated levels of replication stress as compared to both normal cells and many other types of cancers, but the source of this stress is poorly understood. Tumors that harbor elevated levels of replication stress rely on the replication stress and DNA damage-response pathways to retain viability. Understanding the source of the replication stress in Ewing sarcoma may reveal novel therapeutic targets. Ewing sarcomagenesis is complex, and in this review, we discuss the current state of our knowledge regarding elevated replication stress and the DNA damage response in Ewing sarcoma, one contributor to the disease process. We will also describe how these pathways are being successfully targeted therapeutically in other tumor types, and discuss possible novel, evidence based therapeutic interventions in Ewing sarcoma. We hope that this consolidation will spark investigations that uncover new therapeutic targets and lead to the development of better treatment options for Ewing sarcoma patients.