Communications and Marketing

Drug against psoriasis slows down cancer cell growth and metastasis

No. 28 | 12/08/2016

Scientists at the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) are examining a promising agent against cancer of the immune system. In this type of cancer, the tumor cells have lost their ability to respond to signals that cause programmed cell death, or apoptosis. The new substance restores this ability, thus slowing down tumor growth and, above all, metastatic spread.

Immunofluorescence of a cutaneous T cell lymphoma after treatment with DMF (human lymphoma cells were transplanted into the skin of mice). Malignant cells are stained red, dying cells are stained green. In dying tumor cells, the colors superimpose and appear yellow. The huge number of yellow cells indicates that DMF efficiently kills tumor cells.
© Blood, Photo: Anne Schröder/Karin Müller-Decker

Cutaneous T-cell lymphomas present in the skin. They arise from transformed T cells, a type of immune system cells. A special form of this cancer is Sézary syndrome, for which there is no curative treatment to the present day. In patients with this disease, cancerous cells are found not only in the skin but also in the bloodstream from where they can settle in other organs.Cancer researchers know that the malignancy of Sézary syndrome is based primarily on the fact that the cancer cells fail to respond to signals that trigger programmed cell death (apoptosis). This makes treatment of this disease particularly difficult because most anti-cancer drugs rely on causing apoptosis.

Karsten Gülow and his team at the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) in Heidelberg have now succeeded in turning off a specific survival factor, thus driving the cancer cells into apoptosis. In this project, which is funded by the Wilhelm Sander Foundation, the DKFZ researchers collaborated with Jan Nicolay at the Department of Dermatology, Mannheim University Hospital.

"In lymphoma cells, an important cellular 'survival factor' called NFkappaB is permanently activated," Gülow said. "But until now, all tested inhibitors targeting this factor have been too toxic for use as drugs."

For the first time, Gülow, Nicolay and colleagues have now tested an agent called dimethyl fumarate (DMF), which also targets NFkappaB, in cutaneous T-cell lymphoma. A major benefit of this substance is that it is an approved drug for the treatment of multiple sclerosis and psoriasis.

The researchers studied the effect of DMF in T cells that they had isolated from blood samples of patients with Sézary syndrome. They transplanted the tumors cells under the skin of mice, where they grew into tumors. Subsequently, they treated the animals with DMF. After treatment was completed, the tumors grew more slowly and the scientists were able to show that DMF selectively kills tumor cells, leaving healthy T cells unaffected. An even more noteworthy effect was that DMF treatment in the transplanted tumors almost completely suppressed metastatic spread to other organs.

"Our results are very promising," said DKFZ's Peter Krammer. "DMF appears to have at least comparable effectiveness and is better tolerated than most other substances that are used to treat cutaneous lymphomas. Therefore, we have immediately started examining the drug's potential." By now, the investigators have already initiated a clinical trial in collaboration with the working group led by Anne Kuhn from the DKFZ and Sergij Goerdt from the University Dermatology Hospital Mannheim. The trial is supported by the Helmholtz Alliance for Immunotherapy.

Jan P. Nicolay, Karin Müller-Decker, Anne Schroeder, Markus Brechmann, Markus Möbs, Cyrill Géraud, Chalid Assaf, Sergij Goerdt, Peter H. Krammer, Karsten Gülow: Dimethyl fumarate restores apoptosis sensitivity and inhibits tumor growth and metastasis in CTCL by targeting NFκB.

Blood 2016, DOI: 10.1182/blood-2016-01-694117

The German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) with its more than 3,000 employees is the largest biomedical research institute in Germany. At DKFZ, more than 1,000 scientists investigate how cancer develops, identify cancer risk factors and endeavor to find new strategies to prevent people from getting cancer. They develop novel approaches to make tumor diagnosis more precise and treatment of cancer patients more successful. The staff of the Cancer Information Service (KID) offers information about the widespread disease of cancer for patients, their families, and the general public. Jointly with Heidelberg University Hospital, DKFZ has established the National Center for Tumor Diseases (NCT) Heidelberg, where promising approaches from cancer research are translated into the clinic. In the German Consortium for Translational Cancer Research (DKTK), one of six German Centers for Health Research, DKFZ maintains translational centers at seven university partnering sites. Combining excellent university hospitals with high-profile research at a Helmholtz Center is an important contribution to improving the chances of cancer patients. DKFZ is a member of the Helmholtz Association of National Research Centers, with ninety percent of its funding coming from the German Federal Ministry of Education and Research and the remaining ten percent from the State of Baden-Württemberg.

RSS-Feed

Subscribe to our RSS-Feed.

to top