Plant Pathogen Yields Substance to Fight Neuroblastoma
Drug treatment of neuroblastoma, a tumor of the nervous system in children, poses major problems. Therefore, scientists at the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) have been searching for substances that are suitable as a basis for developing better drugs. Now they have found a candidate: HC-toxin, which is isolated from a fungal plant pathogen. The substance from the maize pathogen reprograms neuroblastoma cells in such a way that they behave almost like healthy cells again.
Normally, the fungus Helminthosporium carbonum leads to reduced harvests for maize farmers. Yet a specific constituent of the pathogen, namely HC-toxin, might be very useful for medicine. The substance is used by scientists as a basis for developing a new anti-cancer drug. HC-toxin acts on enzymes known as histone deacetylases (HDACs), which structure the packaging of the genetic material, or DNA. HDAC enzymes change, among others, the histones – proteins around which the DNA is wrapped. Alterations in the packaging of the genetic material are suspected to cause cancer or promote its spread. Therefore, scientists are studying substances that inhibit HDAC enzymes for their ability to fight malignant tumors.
Among these substances is HC-toxin, which has now been investigated by researchers of the Clinical Cooperation Unit "Pediatric Oncology" at the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ). They found out that neuroblastoma cells lose several of their cancer-typical properties when under the influence of the substance: They divide less frequently, show less invasive growth and even their outside appearance resembles healthy nerve cells again. These effects were observed to be stronger than with other HDAC inhibitors investigated previously.
The effect of HC-toxin is presumably based, among other things, on the fact that it promotes the function of an important cellular "cancer brake" known as RB signaling pathway. The investigators found out that the cancer brake was much more active in tumors cells that had been treated with HC-toxin than in untreated cells. They plan to conduct further research to determine whether the substance derived from the maize pathogen is suitable for developing a new drug to fight neuroblastoma.
Neuroblastoma is the second most frequent malignant tumor in children. With an average of 150 new cases diagnosed in Germany each year, neuroblastoma constitutes about seven to eight percent of all childhood cancers. Most affected children are in preschool age, one third are diagnosed under one year of age. Although treatment has been improved over the past few years, chances of recovery from advanced stage neuroblastoma continue to be very low. In addition, the drugs being used often cause serious side effects.
Hedwig E. Deubzer, Volker Ehemann, Frank Westermann, Ralf Heinrich, Gunhild Mechtersheimer, Andreas E. Kulozik, Manfred Schwab, Olaf Witt. Histone deacetylase inhibitor Helminthosporium carbonum (HC)-toxin suppresses the malignant phenotype of neuroblastoma cells. International Journal of Cancer, DOI: 10.1002/ijc23295
The German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) with its more than 2,500 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.