Brain and central nervous system (CNS) tumors represent the most common childhood solid tumors. Comprising 21% of all pediatric cancers, they remain the leading cause of cancer-related mortality and morbidity in childhood. Due to advances in neurosurgical technique, radiation therapy and the use of combination therapy, survival rates have generally increased. However, by cause of the lesion itself, its surgical removal and subsequent treatment, survivors are at high risk of long-term neurocognitive sequelae and secondary cancer. Clearly, improvements in diagnosis and treatment are needed. Accordingly, current treatment is evolving away from conventional, uniform therapy and towards risk-stratified regimens and molecularly-targeted therapies, with the aim of diminishing adverse side effects while minimising the risk of disease recurrence. The multi-functional oncoprotein Y-box binding protein 1 (YB-1) may serve as one such molecular target. Increased YB-1 levels have been reported in a number of pediatric brain tumors, where YB-1 appears to facilitate the advancement of malignant phenotypes. These include proliferation, invasion and resistance to therapy, as well as the maintenance of brain tumor initiating cells. Here we evaluate the current literature and show how YB-1 modulates signalling pathways driving each of these phenotypes. We also review the regulation of YB-1 at a transcriptional, translational, post-translational and sub-cellular level and argue that there is strong and sufficient evidence to support the development of YB-1 as a biomarker and future therapeutic target in childhood brain tumors.

中文翻译：

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Y-box 结合蛋白-1：小儿脑肿瘤中被忽视的靶点？

脑和中枢神经系统 (CNS) 肿瘤是最常见的儿童实体瘤。占所有儿科癌症的 21%，它们仍然是儿童癌症相关死亡率和发病率的主要原因。由于神经外科技术、放射疗法和联合疗法的使用的进步，存活率普遍提高。然而，由于病变本身、手术切除和后续治疗，幸存者面临长期神经认知后遗症和继发性癌症的高风险。显然，需要改进诊断和治疗。因此，目前的治疗正在从传统的、统一的治疗发展到风险分层方案和分子靶向治疗，目的是减少不良副作用，同时最大限度地降低疾病复发的风险。多功能癌蛋白 Y-box 结合蛋白 1 (YB-1) 可以作为一种这样的分子靶标。据报道，在许多儿科脑肿瘤中 YB-1 水平升高，其中 YB-1 似乎促进了恶性表型的发展。这些包括增殖、侵袭和对治疗的抵抗，以及脑肿瘤起始细胞的维持。在这里，我们评估当前的文献并展示 YB-1 如何调节驱动这些表型的信号通路。我们还回顾了 YB-1 在转录、翻译、翻译后和亚细胞水平上的调节，并认为有强有力和充分的证据支持 YB-1 作为儿童大脑生物标志物和未来治疗靶点的发展肿瘤。