Bone Sarcomas in Pediatrics: Progress in Our Understanding of Tumor Biology and Implications for Therapy.
Bone Sarcomas in Pediatrics: Progress in Our Understanding of Tumor Biology and Implications for Therapy.
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DOI：
10.1007/s40272-015-0134-4
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发表时间：
2015-08
期刊：
影响因子：
--
通讯作者：
Hughes DP
中科院分区：
文献类型：
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作者：
Rivera-Valentin RK;Zhu L;Hughes DP
儿童骨肉瘤、骨肉瘤和尤文氏肉瘤是临床医生面临的巨大挑战。虽然不如急性淋巴细胞白血病或脑肿瘤常见，但这些侵袭性癌症占儿童癌症发病率和死亡率的比例不成比例，并且在过去十年中，尽管对各种化疗组合进行了许多大型，复杂和昂贵的试验，但在生存方面几乎没有进展。为了改善骨肉瘤儿童的预后，需要更好地了解这些癌症的生物学，以及利用每种疾病独特生物学的靶向治疗的明智使用。在这里，我们总结了目前的知识状态，受体酪氨酸激酶，细胞内信号通路，骨生物学和生理学，免疫系统，肿瘤微环境的贡献，促进和维持恶性表型。这些观察结果与针对这些机制的治疗方法的综述相结合，重点关注最近或正在进行的临床试验（如果有此类信息）。我们希望，通过更好地了解骨肉瘤和尤文肉瘤的生物学，可以设计和系统地测试合理的组合疗法，从而改善一组迫切需要它们的儿童的结果。
The pediatric bone sarcomas osteosarcoma and Ewing sarcoma represent a tremendous challenge for the clinician. Though less common than acute lymphoblastic leukemia or brain tumors, these aggressive cancers account for a disproportionate amount of the cancer morbidity and mortality in children, and have seen few advances in survival in the past decade, despite many large, complicated, and expensive trials of various chemotherapy combinations. To improve the outcomes of children with bone sarcomas, a better understanding of the biology of these cancers is needed, together with informed use of targeted therapies that exploit the unique biology of each disease. Here we summarize the current state of knowledge regarding the contribution of receptor tyrosine kinases, intracellular signaling pathways, bone biology and physiology, the immune system, and the tumor microenvironment in promoting and maintaining the malignant phenotype. These observations are coupled with a review of the therapies that target each of these mechanisms, focusing on recent or ongoing clinical trials if such information is available. It is our hope that, by better understanding the biology of osteosarcoma and Ewing sarcoma, rational combination therapies can be designed and systematically tested, leading to improved outcomes for a group of children who desperately need them.