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Beyond molecular tumor heterogeneity: protein synthesis takes control.
Oncogene ( IF 6.9 ) Pub Date : 2018-May-01 , DOI: 10.1038/s41388-018-0152-0
Santiago Ramon y Cajal , Josep Castellvi , Stefan Hümmer , Vicente Peg , Jerry Pelletier , Nahum Sonenberg

One of the daunting challenges facing modern medicine lies in the understanding and treatment of tumor heterogeneity. Most tumors show intra-tumor heterogeneity at both genomic and proteomic levels, with marked impacts on the responses of therapeutic targets. Therapeutic target-related gene expression pathways are affected by hypoxia and cellular stress. However, the finding that targets such as eukaryotic initiation factor (eIF) 4E (and its phosphorylated form, p-eIF4E) are generally homogenously expressed throughout tumors, regardless of the presence of hypoxia or other cellular stress conditions, opens the exciting possibility that malignancies could be treated with therapies that combine targeting of eIF4E phosphorylation with immune checkpoint inhibitors or chemotherapy.

中文翻译:

超越分子肿瘤的异质性:蛋白质合成可以控制。

现代医学面临的艰巨挑战之一是对肿瘤异质性的理解和治疗。大多数肿瘤在基因组和蛋白质组学水平上均显示出肿瘤内异质性,对治疗靶标的反应有显着影响。与治疗靶标相关的基因表达途径受缺氧和细胞应激影响。然而,无论是否存在缺氧或其他细胞应激条件,靶标如真核生物起始因子(eIF)4E(及其磷酸化形式p-eIF4E)通常在整个肿瘤中均表达,这一发现为恶性肿瘤带来了令人兴奋的可能性可以采用将靶向eIF4E磷酸化与免疫检查点抑制剂或化学疗法相结合的疗法进行治疗。
更新日期:2018-02-21
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