The therapeutic potential of targeting the PI3K pathway in pediatric brain tumors.
The therapeutic potential of targeting the PI3K pathway in pediatric brain tumors.
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DOI：
10.18632/oncotarget.13781
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发表时间：
2017-01-10
期刊：
影响因子：
--
通讯作者：
Grundy RG
中科院分区：
文献类型：
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作者：
Rogers HA;Estranero J;Gudka K;Grundy RG
中枢神经系统肿瘤是儿童中最常见的癌症类型，也是癌症相关死亡的主要原因。因此，需要开发新的治疗方法。大规模的分析研究已经开始鉴定可以在治疗上靶向的改变，包括磷酸肌醇3-激酶（PI 3 K）信号通路，其是癌症中最常见的活化通路之一，具有许多正在临床开发的抑制剂。PI 3 K信号已被证明是异常激活，在许多小儿中枢神经系统肿瘤。临床前分析支持PI 3 K信号传导在控制肿瘤生长、存活和迁移以及增强当前治疗的细胞毒性作用中的作用。基于这一证据，靶向PI 3 K信号传导的药物已开始在儿科癌症患者的临床试验中进行测试。总体而言，靶向PI 3 K途径是治疗儿科中枢神经系统肿瘤的一种有前途的策略。在这篇综述中，我们研究了儿童CNS肿瘤中PI 3 K通路的遗传改变及其所起的病理作用，并总结了目前支持使用PI 3 K通路抑制剂治疗这些肿瘤的临床前和临床数据。
Central nervous system tumors are the most common cancer type in children and the leading cause of cancer related deaths. There is therefore a need to develop novel treatments. Large scale profiling studies have begun to identify alterations that could be targeted therapeutically, including the phosphoinositide 3-kinase (PI3K) signaling pathway, which is one of the most commonly activated pathways in cancer with many inhibitors under clinical development. PI3K signaling has been shown to be aberrantly activated in many pediatric CNS neoplasms. Pre-clinical analysis supports a role for PI3K signaling in the control of tumor growth, survival and migration as well as enhancing the cytotoxic effects of current treatments. Based on this evidence agents targeting PI3K signaling have begun to be tested in clinical trials of pediatric cancer patients. Overall, targeting the PI3K pathway presents as a promising strategy for the treatment of pediatric CNS tumors. In this review we examine the genetic alterations found in the PI3K pathway in pediatric CNS tumors and the pathological role it plays, as well as summarizing the current pre-clinical and clinical data supporting the use of PI3K pathway inhibitors for the treatment of these tumors.