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Abstract：
The prognosis for patients with non‑small cell lung cancer (NSCLC), a cancer type which represents 85% of all lung cancers, is poor with a 5‑year survival rate of 19%, mainly because NSCLC is diagnosed at an advanced and metastatic stage. Despite recent therapeutic advancements, ~50% of patients with NSCLC will develop brain metastases (BMs). Either surgical BM treatment alone for symptomatic patients and patients with single cerebral metastases, or in combination with stereotactic radiotherapy (RT) for patients who are not suitable for surgery or presenting with fewer than four cerebral lesions with a diameter range of 5‑30 mm, or whole‑brain RT for numerous or large BMs can be administered. However, radioresistance (RR) invariably prevents the action of RT. Several mechanisms of RR have been described including hypoxia, cellular stress, presence of cancer stem cells, dysregulation of apoptosis and/or autophagy, dysregulation of the cell cycle, changes in cellular metabolism, epithelial‑to‑mesenchymal transition, overexpression of programmed cell death‑ligand 1 and activation several signaling pathways; however, the role of the Hippo signaling pathway in RR is unclear. Dysregulation of the Hippo pathway in NSCLC confers metastatic properties, and inhibitors targeting this pathway are currently in development. It is therefore essential to evaluate the effect of inhibiting the Hippo pathway, particularly the effector yes‑associated protein‑1, on cerebral metastases originating from lung cancer.
摘要：
非小细胞肺癌（NSCLC）患者的预后，占所有肺癌85%的癌症类型，较差，5年生存率为19%，主要是因为NSCLC在晚期和转移阶段被诊断。尽管最近的治疗进展，约50%的NSCLC患者会发生脑转移(BMs)。对于有症状的患者和单个脑转移患者，单独进行手术BM治疗，或与立体定向放射治疗（RT）相结合，用于不适合手术或表现为小于四个直径范围为5-30mm的脑部病变的患者，或全脑RT可以用于许多或大型BM。然而,辐射抗性(RR)总是阻止RT的作用。已经描述了RR的几种机制，包括缺氧，细胞应激，癌症干细胞的存在，细胞凋亡和/或自噬失调，细胞周期失调，细胞代谢的变化，上皮-间质转化，程序性细胞死亡配体1的过表达和激活几种信号通路；然而，Hippo信号通路在RR中的作用尚不清楚。非小细胞肺癌中Hippo途径的失调赋予转移特性，和针对该途径的抑制剂目前正在开发中。因此，必须评估抑制Hippo途径的效果，特别是效应基因相关蛋白-1，对源自肺癌的脑转移。
