癌症驱动信号导致高风险神经母细胞瘤

研究人员已经发现了异常分子信号和生物事件的细节，这是一种高风险的儿童癌症神经母细胞瘤的形成。他们的目标是使用这些研究结果，制定更有效的针对性治疗。

“当我们提高我们的知识，不同的生物学通路的基因和蛋白在这种复杂的疾病，我们能更好地制定相应的药物组合来治疗神经母细胞瘤，”共同作者Sharon J。迪斯，博士，一个 儿科癌症 研究员 费城儿童医院（CHOP）。迪斯和他的同事以信令网络涉及三个致癌基因： LIN28B， 跑 和 AURKA。

该研究发表在今天的 在线癌细胞, and will appear in print on Nov。 9。

Diskin’s collaborators, both from CHOP, include pediatric oncologists John M。 Maris, MD, her co-senior author, and first author Robert Schnepp, MD, PhD。

A solid tumor of the peripheral nervous system， neuroblastoma usually occurs in the chest or abdomen。 It accounts for 7 percent of all childhood cancers, and 10 to 15 percent of all childhood cancer deaths。 Although survival rates have improved over the years, more effective treatments are needed for high-risk subsets of neuroblastoma。

Researchers at CHOP and other centers have discovered a variety of genes contributing to this complex disease, and continue to pursue innovative therapies。

研究建立在以前的发现，探索特定的机制

目前的研究是建立在一个 2012发现迪斯，Maris及其同事 表明变异 LIN28B raised the risk of neuroblastoma。 The gene was already known to play roles in different cancers, but their study was the first to link it to neuroblastoma。

新的研究探讨具体的机制， LIN28B drives neuroblastoma。 The research team performed cell analyses of 250 tumor samples from neuroblastoma patients, in addition to studies in animal models。

他们发现，在 变种LIN28B 基因产生异常信号，另一个叫 调节基因跑。 The 跑 gene, in turn, becomes overactive and produces higher levels of the 跑 protein, causing cells to grow out of control in tumors。

Acting in both direct and indirect ways， LIN28B also blocks tumor suppressor genes that normally put the brakes on cancer。 The research suggests that signals originating in LIN28B 最终推动另一个基因称为 AURKA, already known to play key roles in neuroblastoma and other cancers。

All three genes， LIN28B， 跑，和 AURKA , function as oncogenes­—genes known to drive cancer when affected by genetic changes。 In parsing the complex interplay of genes and proteins acting in this signaling network, the researchers say these pathways represent potential targets for future neuroblastoma treatments。

“In preclinical and clinical studies, some existing anticancer drugs show desired effects against components of these pathways,” said first author Robert Schnepp, MD, PhD。 He added, “Our research offers opportunities to develop possible drug combinations to be tested in future clinical trials。”

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