Researchers at the University of Eastern Finland and Eberhard Karls Universität Tübingen have discovered a new molecular mechanism that can be used to inhibit the growth of hepatocellular carcinoma, which is the most common liver cancer. The findings were published in Nature Medicine .
The study found that mouse and human liver cancer in which the function of the protein p53 is disturbed or inhibited is dependent on the interaction between the Aurora kinase A (AURKA) and MYC proteins. Interfering the AURKA protein with a specific drug molecule inhibits this interaction and causes cancer cells to die.
With the help of computer-aided molecular modelling, the Pharmaceutical & Medicinal Chemistry research group at the University of Eastern Finland analysed interactions between the AURKA and MYC proteins. Molecular modelling also helped understand why only certain drug molecules inhibit the AURKA-MYC interaction, while others have no impact on it at all. Furthermore, molecular modelling made it possible to predict whether a certain drug molecule can inhibit the AURKA-MYC interaction or not.
Currently, no effective treatments for advanced liver cancer exist. By specifically targeting the AURKA protein, it may be possible to efficiently prevent the growth of p53 altered liver cancer. The findings of the study can be made use of in the development of treatments for patients with this cancer type.
Following the discovery of this new potential treatment target in liver cancer, the University of Eastern Finland and Eberhard Karls Universität Tübingen have launched a project focusing on the development of a new cancer drug. Several universities and research institutes in Germany and France have also participated in this research.
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The study was funded by the Academy of Finland, the EU, and the Deutsche Forschungsgemeinschaft, DFG.
The Pharmaceutical & Medicinal Chemistry research group (PMC) operates on the Kuopio Campus of the University of Eastern Finland. Renowned internationally, the cross-disciplinary PMC group is an expert in the fields of medicinal chemistry and computer-aided drug design. The PMC group's research addresses the development of novel cancer drugs and antibiotics in particular, as well as the targeting of drugs at the central nervous system, and high-level analytics.
For further information, please contact: Professor Antti Poso, University of Eastern Finland and Eberhard Karls Universität Tübingen, tel. +358403552462, antti.poso@uef.fi
Research article:
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. A MYC-aurora kinase A protein complex represents an actionable drug target in p53-altered liver cancer. Nature Medicine (2016).
Published online 23 May 2016. doi:10.1038/nm.4107
Nature Medicine