In almost all cases of colon cancer, a specific gene is mutated – this offers opportunities to develop broadly effective therapeutic approaches. Research teams in Würzburg have taken this a step further.
In 90 percent of all cases of colon cancer, the tumour cells have one thing in common: the APC gene is mutated. Research groups at Julius-Maximilians-Universität (JMU) Würzburg in Bavaria, Germany, were looking for targets in these cells that could be used to destroy the cells.
"We wanted to find genes that are only important for the survival of cells with APC mutations, but not for healthy cells," explains Dr. Armin Wiegering, head of a junior research group at the JMU Biocentre and physician in surgery at Würzburg University Hospital.
The search for a needle in a haystack was successful. The research teams now report this in the journal Nature Cell Biology: If they inhibited the gene called eIF2B5, the mutated colon cancer cells died of programmed cell death – a self-destruction programme with which the organism normally disposes of damaged or aged cells. Healthy cells, on the other hand, were able to cope with the inhibition of the gene without any impairment.
Possible point of attack for treatment
"We have thus identified a very specific Achilles heel of APC-mutated tumours," says Professor Martin Eilers, cancer researcher at the Biocentre. We now know of a site where newly developed antitumour drugs might be able to have a very targeted effect.
The efficacy of an elF2B5 inhibition was shown in animal experiments. If the gene is not fully active in mice, they do not develop colon cancer so quickly and survive much longer if they do. The researchers also experimented with organoids. These are miniature tumours that are cultivated in the laboratory from the cancer tissue of patients. If the amount of elF2B5 was reduced, the organoids died.
Further genes will be investigated
Next, the researchers want to investigate further genes in colon cancer cells – because elF2B5 is only one of five subunits of the larger eIF2B gene complex. "We also want to characterize the other subunits and see if we can also find a specificity here," Wiegering announces. We will then establish a method to degrade eIF2B5 in cancer cells. If this is successful, it might lead to a new option for therapies.
Info box: Colon cancer
Colon cancer is one of the three most common tumour diseases. About six percent of all people in Germany fall ill with it in the course of their lives; about half of those affected die from the consequences of the tumour. Since more than 90 percent of all colon tumours show an APC mutation, research at JMU could lead to a very broad, new therapeutic approach.
Sponsors and cooperation partners
This work was funded by the Interdisciplinary Centre for Clinical Research IZKF Würzburg, the Else Kröner Fresenius Foundation, the German Research Foundation, and the European Union.
The following institutions were significantly involved in the publication in Nature Cell Biology: the Department of General, Visceral, Transplantation, Vascular and Pediatric Surgery of the University Hospital Würzburg, the Chair of Biochemistry and Molecular Biology at the JMU Biocentre, the JMU Institute of Pathology and the Beatson Institute in Glasgow, Scotland.
PD Dr. Armin Wiegering, University of Würzburg, firstname.lastname@example.org
A MYC-GCN2-eIF2 α negative feedback loop limits protein synthesis to prevent MYC-dependent apoptosis in colorectal cancer. Nature Cell Biology, November 4, 2019, DOI 10.1038/s41556-019-0408-0
Robert Emmerich | Julius-Maximilians-Universität Würzburg
How cells stick together tightly
05.11.2019 | Max-Planck-Institut für molekulare Zellbiologie und Genetik
Helping hands from within: Live-in bacteria protect plants against infections
04.11.2019 | Netherlands Institute of Ecology (NIOO-KNAW)
An international research group has observed new quantum properties on an artificial giant atom and has now published its results in the high-ranking journal Nature Physics. The quantum system under investigation apparently has a memory - a new finding that could be used to build a quantum computer.
The research group, consisting of German, Swedish and Indian scientists, has investigated an artificial quantum system and found new properties.
Researchers at the U.S. Department of Energy's (DOE) Argonne National Laboratory have reported a new mechanism to speed up the charging of lithium-ion...
Northwestern University chemists have used visible light and extremely tiny nanoparticles to quickly and simply make molecules that are of the same class as...
Almost everyone uses nanometer-sized alumina these days - this mineral, among others, constitutes the skeleton of modern catalytic converters in cars. Until now, the practical production of nanocorundum with a sufficiently high porosity has not been possible. The situation has changed radically with the presentation of a new method of nanocorundum production, developed as part of a German-Polish cooperation of scientists from Mülheim an der Ruhr and Cracow.
High temperatures and pressures, processes lasting for even dozens of days. Current methods of producing nanometer-sized alumina, a material of significant...
Quantum mechanics is embracing patterns of light to create an alphabet that can be leveraged to build a light-based quantum network
Structured light is a fancy way to describe patterns or pictures of light, but deservedly so as it promises future communications that will be both faster and...
05.11.2019 | Event News
30.10.2019 | Event News
02.10.2019 | Event News
05.11.2019 | Information Technology
05.11.2019 | Life Sciences
05.11.2019 | Earth Sciences