Death Blow to Cancer Cells

The principle sounds surprisingly simple: Like all other body cells, cancer cells derive the energy required for maintaining their metabolism from nutrients. At the same time, they use a major part of the nutrients for the construction of cell components, cell division and proliferation. Since nutrients are necessarily limited, there is a kind of "guard" in the cells, which always makes sure that sufficient resources are allocated for both of the tasks and which limits cell growth if the cell does not have access to sufficient energy for normal metabolic processes.

Publication in Nature

What happens if this "guard" is prevented from doing its work? This has been examined by Professor Martin Eilers and Dr. Daniel J. Murphy of the Biocenter at the University of Würzburg in cooperation with an international team. Their research is published in the current issue of the prestigious journal Nature.

The result: "If the cancer cell is not given any feedback when its energy balance has gone awry, it wastes all the resources from the nutrients on cell growth and cell division," explains Martin Eilers, chair of the Department for Biochemistry and Molecular Biology. The cell eventually exhausts itself to the point that there is no energy left for the normal metabolic processes within the cell. In fact, the cancer cell dies without the warning signal of the "guard", as the researchers were able to demonstrate.

The researchers came across this "guard" by chance. In large-scale serial studies, they selectively switched off so-called kinases, a specific kind of enzyme, and examined the consequences. With the ARK5 kinase, they hit the jackpot. "This kinase is a suitable target for potential new therapeutic drugs," says Daniel J. Murphy, group leader at the Department of Physiological Chemistry II. In all experiments, the cancer cells have proven vulnerable at this point.

At the same time – much to the surprise of the scientists – the tests showed that normal cells are largely unaffected by an inhibition of this kinase. "Why this is the case, we do not fully understand in every detail," says Murphy. And there might be some effects at this point that will only become visible over the long-term. Nevertheless: "With respect to a potential therapy, it is important that normal cells differ from cancer cells at this point," Murphy explains.

A scientific breakthrough

Does this represent a breakthrough in cancer treatment? The scientists still hesitate to give a definite answer to this question. "At the very least, it is a new concept," says Martin Eilers. "A completely new way to approach the problem," adds Daniel J. Murphy. Whether this leads to a breakthrough for cancer treatment or not, only time will tell. In any case, the method has proven effective for bowel cancer cells in cell culture and in animal experiments. But it has yet to be determined in further studies, to which extent other types of cancer cells can be driven to death by this method.

In any case, the pharmaceutical industry has already shown great interest in the findings of the Würzburg researchers; the cooperation will start soon. Furthermore, as Eilers points out, the Comprehensive Cancer Center of the University of Würzburg is available as a suitable partner for conceptual analysis in further pre-clinical studies and for future testing of a potential treatment at the bedside.

However, both scientists warn against high hopes on the treatment, which may be placed too early: There are still a lot of studies to be done until the final verdict can be reached on the new approach to cancer treatment and it generally takes several years until a newly developed drug is ready for the market – if indeed the drug makes it to this stage. "There is always the risk that the cells acquire a resistance to a drug," Eilers cautions against excessive euphoria.

Nevertheless: At the moment, the two scientists are optimistic about their discovery, for the scientific breakthrough has undoubtedly been achieved.

Deregulated MYC expression induces dependence upon AMPK-related kinase 5. Lidan Liu, Jannes Ulbrich, Judith Müller, Torsten Wüstefeld, Lukas Aeberhard, Theresia R. Kress, Nathiya Muthalagu, Lukas Rycak, Ramona Rudalska, Roland Moll, Stefan Kempa, Lars Zender, Martin Eilers & Daniel J. Murphy. doi: 10.1038/nature10927

Contact person

Prof. Dr. Martin Eilers, T: (0931) 31-84111
e-mail: Martin.Eilers@biozentrum.uni-wuerzburg.de

Dr. Daniel Murphy, T: (0931) 31-88069
e-mail: daniel.murphy@biozentrum.uni-wuerzburg.de