MET signaling promotes DNA repair and radiation resistance in glioblastoma stem-like cells.
MET signaling promotes DNA repair and radiation resistance in glioblastoma stem-like cells.
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DOI：
10.21037/atm.2017.01.67
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发表时间：
2017-02
影响因子：
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通讯作者：
P. Todorova;B. Mukherjee;S. Burma
中科院分区：
文献类型：
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作者：
P. Todorova;B. Mukherjee;S. Burma
胶质母细胞瘤（GBM）是一种原发性脑肿瘤，其特征是侵袭性生长和快速复发。它们是成人和儿童患者癌症相关死亡的主要原因 (1,2)。尽管在了解神经胶质瘤发生的遗传和分子驱动因素方面取得了相当大的成功，但目前的护理标准充其量只能提供短暂的缓解。新诊断的GBM患者接受减瘤手术和辅助放疗联合替莫唑胺化疗后，平均生存期为14.6个月（3）。尽管采取了积极的治疗方案，但患者总是死于复发相关的死亡。当前实验和标准治疗不可避免的失败归因于 GBM 的两个关键特征。首先，肿瘤间和肿瘤内显着的异质性阻碍了靶向单一疗法的成功应用 (4,5)。其次，难以治疗的独特 GBM 癌症干细胞的存在可能会导致肿瘤复发 (5,6)。这些存在于原发性 GBM 中的弹性干细胞样细胞通过电离辐射 (IR) 和/或替莫唑胺进行积极选择，并且经常进行基因改变 (7,8)。结果，复发的肿瘤不再对放疗或化疗做出反应。迫切需要鉴定原发性肿瘤中的此类耐药细胞，了解治疗耐药性的分子基础，并制定有效靶向原发性或复发性肿瘤中这些细胞的策略。
Glioblastomas (GBMs) are primary brain tumors characterized by aggressive growth and rapid recurrence. They represent a leading cause of cancer-related deaths both in adult and pediatric patients (1,2). Despite the considerable success in understanding the genetic and molecular drivers of gliomagenesis, the current standard of care provides, at best, a transient remission. Newly-diagnosed GBM patients, who receive de-bulking surgery and adjuvant radiotherapy combined with temozolomide chemotherapy, have an average survival of 14.6 months (3). Invariably, patients succumb to recurrence-related death despite aggressive treatment regimens. The inevitable failure of current experimental and standard treatments has been attributed to two key features of GBM. First, the marked inter- and intra-tumoral heterogeneity prevents successful application of targeted monotherapies (4,5). Second, the existence of distinct GBM cancer stem cells which are refractory to treatment may drive tumor recurrence (5,6). These resilient stem-like cells present in the primary GBM are positively selected for, and oftentimes genetically altered, by ionizing radiation (IR) and/or temozolomide (7,8). As a result, the recurrent tumors no longer respond to radiation or chemotherapy. There is an urgent need to identify such therapy-resistant cells in the primary tumor, understand the molecular basis of therapy resistance, and develop strategies to effectively target these cells in primary or recurrent tumors.