Division of Brain Tumor Translational Research, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan; Department of Neurosurgery, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan.
Division of Brain Tumor Translational Research, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.
Semin Cancer Biol. 2019 Oct;58:118-129. doi: 10.1016/j.semcancer.2019.01.004. Epub 2019 Jan 24.
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.
尽管几十年来外科技术和辅助疗法不断发展，但胶质母细胞瘤（GBM）的治疗效果仍然不佳。导致神经胶质瘤预后不良的主要原因是可切除的肿瘤组织有限（为了保护脑功能），并且残留肿瘤通常对放疗和化疗有抗性。因此，克服残留肿瘤对辅助治疗的抗性是治疗神经胶质瘤的当务之急。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神经胶质瘤中相互关联，这些信息可能有助于阐明哪些分子或信号在抵抗放疗或化疗方面起关键作用，将其作为针对难治性神经胶质瘤的潜在新的治疗靶点。在这篇综述中，我们主要基于队列研究或最近的证据，总结了调控神经胶质瘤生物学的分子网络的最新认识，重点介绍了神经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耐药性。
