Signal transduction pathways and resistance to targeted therapies in glioma
Signal transduction pathways and resistance to targeted therapies in glioma
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DOI：
10.1016/j.semcancer.2019.01.004
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发表时间：
2019-10-01
影响因子：
14.5
通讯作者：
Ichimura, Koichi
中科院分区：
文献类型：
--
作者：
Tomiyama, Arata;Ichimura, Koichi
虽然手术技术和辅助治疗已经经历了几十年的逐步发展，治疗胶质母细胞瘤（GBM）的治疗结果仍然很差。胶质瘤预后不良的主要原因是可切除的肿瘤组织有限（以保留脑功能），并且残留的肿瘤通常对放疗和化疗有抵抗力。因此，克服残留肿瘤对辅助治疗的耐药性是胶质瘤治疗的迫切需要。最近对GBM遗传改变的大型队列研究表明，遗传信息和细胞内分子信号在胶质瘤中是网络化的，这些信息可能有助于澄清哪些分子或信号在抵抗放射或化疗中起重要作用，突出它们作为难治性胶质瘤的潜在新治疗靶点。在这篇综述中，我们总结了目前对控制胶质瘤生物学的分子网络的理解，主要基于队列研究或最近的证据，重点是胶质瘤中的细胞内信号分子如何相互关联并调节对当前治疗的不应性。
Although surgical techniques and adjuvant therapies have undergone progressive development for decades, the therapeutic outcomes for treating glioblastoma (GBM) remain poor. The main reasons for the poor prognosis of gliomas are that limited tumor tissue that can be resected (to preserve brain functions) and that residual tumors are often resistant to irradiation and chemotherapy. Therefore, overcoming the resistance of residual tumors against adjuvant therapy is urgently needed for glioma treatment. Recent large cohort studies of genetic alterations in GBM demonstrated that both genetic information and intracellular molecular signaling are networked in gliomas and that such information may help clarify which molecules or signals serve essential roles in resistance against radiation or chemotherapy, highlighting them as potential novel therapeutic targets against refractory gliomas. In this review, we summarize the current understanding of molecular networks that govern glioma biology, mainly based on cohort studies or recent evidence, with a focus on how intracellular signaling molecules in gliomas associate with each other and regulate refractoriness against current therapy.