Drug against psoriasis slows down cancer cell growth and metastasis
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
With more than 3,000 employees, the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) is Germany’s largest biomedical research institute. DKFZ scientists identify cancer risk factors, investigate how cancer progresses and develop new cancer prevention strategies. They are also developing new methods to diagnose tumors more precisely and treat cancer patients more successfully. The DKFZ's Cancer Information Service (KID) provides patients, interested citizens and experts with individual answers to questions relating to cancer.
To transfer promising approaches from cancer research to the clinic and thus improve the prognosis of cancer patients, the DKFZ cooperates with excellent research institutions and university hospitals throughout Germany:
The DKFZ is 90 percent financed by the Federal Ministry of Education and Research and 10 percent by the state of Baden-Württemberg. The DKFZ is a member of the Helmholtz Association of German Research Centers.
