东芬兰大学的研究人员和蒂宾根大学的研究人员发现了一个新的分子机制，该分子机制可用于抑制肝细胞癌的生长，这是一种最常见的肝癌。这项研究结果发表在《Nature Medicine》杂志上。
通过研究发现，小鼠和人类肝癌的功能蛋白质p53蛋白通过极光激酶(AURKA)和MYC蛋白质之间的交互作用而扰或抑制。用特定的药物分子干扰AURKA蛋白来抑制这种交互作用，最终导致肝癌细胞死亡。
借助计算机辅助分子模型的作用， 东芬兰大学制药和药物化学研究小组分析了AURKA蛋白质和MYC蛋白质之间的相互作用。这种分子模型也会帮助人们理解为什么只有某些药物分子可以抑制AURKA蛋白质和MYC蛋白质之间的交互作用，而其它药物对它们则没有影响。此外，该分子模型可预测某种药物分子是否可以抑制AURKA蛋白质和MYC蛋白质之间的交互作用。
MYC癌基因蛋白保护绝大多数人类肿瘤，一直被人们认为无药可治的。通过体内 shRNA的直接筛选，我们的研究发现在肿瘤抑制基因编*****蛋白p53(小鼠TrP53和人类Trp53)中肝癌细胞产生了突变。
目前，还没有有效的药物可治疗晚期肝癌。通过专门靶向研究AURKA蛋白质，可以有效防止p53的生长从而抑制肝癌发展。这项研究的发现可以用在这种癌症患者治疗的发展方向上。
针对这种靶向治疗肝癌的新方法， 东芬兰大学和蒂宾根大学启动了新抗癌药物发展的项目。德国和法国的几所大学和研究机构也参与了这项研究。
doi:10.1038/nm.4107
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A MYC–aurora kinase A protein complex represents an actionable drug target in p53-altered liver cancer
Daniel Dauch, Ramona Rudalska, Giacomo Cossa, Jean-Charles Nault, Tae-Won Kang, Torsten Wuestefeld, Anja Hohmeyer, Sandrine Imbeaud, Tetyana Yevsa, Lisa Hoenicke, Tatu Pantsar, Przemyslaw Bozko, Nisar P Malek, Thomas Longerich, Stefan Laufer, Antti Poso, Jessica Zucman-Rossi, Martin Eilers &Lars Zender
MYC oncoproteins are involved in the genesis and maintenance of the majority of human tumors but are considered undruggable. By using a direct in vivo shRNA screen, we show that liver cancer cells that have mutations in the gene encoding the tumor suppressor protein p53 (Trp53 in mice and TP53 in humans) and that are driven by the oncoprotein NRAS become addicted to MYC stabilization via a mechani mediated by aurora kinase A (AURKA). This MYC stabilization enables the tumor cells to overcome a latent G2/M cell cycle arrest that is mediated by AURKA and the tumor suppressor protein p19ARF. MYC directly binds to AURKA, and inhibition of this protein–protein interaction by conformation-changing AURKA inhibitors results in subsequent MYC degradation and cell death. These conformation-changing AURKA inhibitors, with one of them currently being tested in early clinical trials, suppressed tumor growth and prolonged survival in mice bearing Trp53-deficient, NRAS-driven MYC-expressing hepatocellular carcinomas (HCCs). TP53-mutated human HCCs revealed increased AURKA expression and a positive correlation between AURKA and MYC expression. In xenograft models, mice bearing TP53-mutated or TP53-deleted human HCCs were hypersensitive to treatment with conformation-changing AURKA inhibitors, thus suggesting a therapeutic strategy for this subgroup of human HCCs.
