Tumor Therapy: New Approaches to Fight Cancerous Diseases
The Lichtenberg Professor Dr. Christian Reinhardt and his team found out that the growth of specific tumors can be prevented by inhibiting two certain enzymes.
Despite many advances in medicine, cancer remains the most common cause of death in Germany and the Western World. As the further development of diagnostic tests and treatment is essential for patients, researchers are continuously looking for innovative approaches to targeted cancer therapy. Scientists in Cologne led by
Lichtenberg Professor
Dr. Christian Reinhardt from the
University of Cologne have now identified such a new approach through the molecular characterization of tumor cells. An international team of researchers from Germany, Denmark and England was involved in the study, which has been published on July 2, 2015, in the high impact journal Cell.
The study shows in detail that tumor cells and cancers with a mutation in the KRAS gene depend on two distinct enzymes: Chk1 and MK2. The KRAS gene is one of the most commonly mutated genes appearing in human cancer cells. Mutated KRAS is found in almost all pancreatic cancers, and about one-third of lung and colorectal cancers. Analyses demonstrate that KRAS mutations lead to massively increased cell growth. But the very rapid proliferation of cancer cells causes problems during DNA duplication which has to take place prior to every cell division. The data from the scientists show that KRAS-mutated cancer cells rely on MK2 and Chk1 enzyme function for error-free duplication of their DNA.
New Treatments can be Developed
The dependence on MK2 and Chk1 distinguishes KRAS-mutant cancer cells from healthy tissue, which is capable of duplicating DNA without these particular enzymatic functions. And the new therapeutic approach is based on this very difference between cancer cells and normal tissue. The research team has proved that tumor cells and cancers with KRAS mutations respond very well to combination therapy with Chk1 and MK2 inhibitors. Normal tissue, on the other hand, tolerates the combination therapy well and has very little in the way of adverse reactions. A combined pharmacological inhibition of Chk1 and MK2 is a therapeutic strategy that could be used specifically for treating KRAS-mutated cancers. "Chk1/MK2 inhibition works specifically in KRAS-mutant cancer cells. Normal tissue isn't really affected, because healthy cells don't contain KRAS genes that have undergone mutation," summarizes
Dr. Felix Dietlein, lead author of the publication, the therapeutic concept.
Prof. Michael Hallek, Head of the Department of Internal Medicine I at the University of Cologne, adds another fact: "MK2 is an enzyme that has been investigated in depth for some time, as its function seems to have a role in the development of rheumatoid disease. Chk1 has also been closely scrutinized in recent years, and the first clinical trials of various Chk1 inhibitors are now underway. These fascinating findings may provide treating physicians with an effective new tool for treating KRAS-mutant cancers in the near future." Work on this project was funded by the German Research Foundation, German Cancer Aid, and the Volkswagen Foundation.
Information on the Publication
Felix Dietlein, Bastian Kalb, Mladen Jokic, Elisa M. Noll, Alexander Strong, Lars Tharun, Luka Ozretić, Helen Künstlinger, Kato Kambartel, Winfried J. Randerath, Christian Jüngst, Anna Schmitt, Alessandro Torgovnick, André Richters, Daniel Rauh, Florian Siedek, Thorsten Persigehl, Cornelia Mauch, Jirina Bartkova, Allan Bradley, Martin R. Sprick, Andreas Trumpp, Roland Rad, Dieter Saur, Jiri Bartek, Jürgen Wolf, Reinhard Büttner, Roman K. Thomas, H. Christian Reinhardt. 2015. A Synergistic Interaction between Chk1- and MK2 Inhibitors in KRAS-Mutant Cancer Cell, Volume 162, Issue 1, 2 July 2015, Pages 146–159
Link to the publication in Cell.
Backgroung Lichtenberg Professorships
The Foundation combines support both for individual researchers as well as institutions via the funding initiative
"Lichtenberg Professorships". Outstanding young researchers are offered a tenure-track at a university of their choice in Germany, enabling them to carry out independent research in innovative and interdisciplinary areas for longer periods of time.
