vom 28.02.2020

Rare cancer: key feature aids diagnosis and therapy for a specific form of nerve sheath tumor

Nerve sheath tumors are not only rare but also diverse and often difficult to treat. Using molecular analyzes, scientists and doctors have now been able to identify a genetic change that can be used to determine a specific subform of nerve sheath tumors. The affected gene is known as ERBB2 or HER2 and has so far mainly been implicated in breast cancer. For one patient in the NCT / DKTK MASTER Program, this gene modification opened up a new treatment option.

The National Center for Tumor Diseases (NCT) Heidelberg is a joint institution of the German Cancer Research Center (DKFZ), Heidelberg University Hospital (UKHD) and German Cancer Aid (DKH).

Nerve sheath tumors are rare and mostly benign tumors arising from cells that envelop the peripheral nerves. Patients affected experience disturbance of sensation, pain, weakness, and sometimes even paralysis. The most common neural sheath tumor is schwannoma. In schwannomatosis, patients develop numerous tumors along the peripheral nerves. Other forms are neurofibromas, perineurinomas, and nerve sheath myxomas. Treating these tumors is often challenging as many of the subforms are poorly understood. There is also a distinct lack of any established drug treatments.

In some cases, patients suffer from a so-called hybrid tumor that has features from both neurofibroma and schwannoma tumor types. Scientists and doctors have examined the genetic makeup of such a hybrid tumor in a 30-year-old patient. The genetic analysis was carried out within the NCT / DKTK MASTER (Molecularly Aided Stratification for Tumor Eradication) Program, which is headed by the Directors of the National Center for Tumor Diseases (NCT) in Heidelberg and Dresden, Stefan Fröhling and Hanno Glimm, and focuses on young patients with advanced cancer and patients with rare tumors (www.nct-heidelberg.de/master).

The researchers discovered that the tumor harbored a change in a gene that provides the blueprint for the so-called ERRB2 receptor. ERRB2, also known as HER2, is a surface protein to which growth factors bind and stimulate cell division. The receptor is prominent on breast cancer cells and is used in this disease as the target for individually tailored treatment with, for example, the tyrosine kinase inhibitor lapatinib. “Our patient received lapatinib as a result of the identification of the mutation. During therapy, tumor growth slowed down, nerve pain was relieved, and the disease stabilized over the longer term,” reports Michael Ronellenfitsch, first author of the paper and Senior Consultant at the Institute of Neurooncology, University Hospital Frankfurt.

In order to make the results from this individual case usable for other patients, the researchers worked in close cooperation with Albrecht Stenzinger, Head of the Center for Molecular Pathology at the Institute of Pathology at Heidelberg University Hospital (UKHD), including 14 other patients with a hybrid tumor. Since the disease is very rare, patients from the centers of the German Cancer Consortium (DKTK) Heidelberg, Tübingen, and Frankfurt were also included. "Based on this individual case, we were able to use the NCT / DKTK MASTER network and targeted molecular analysis to identify further nerve sheath tumors with ERBB2 mutations that had developed from non-hereditary schwannomatosis," reports Albrecht Stenzinger.

Using this concept of collaboration across disciplines and locations, which in my view is without alternative in the field of rare tumors, we have been able to show that ERBB2 mutations occur frequently in a specific subset of nerve sheath tumors," says Fröhling, who heads the Division of Translational Medical Oncology at the German Cancer Research Center (DKFZ). “This result opens up another therapy option for a relevant fraction of patients with this rare disease. In addition, the mutation is an important criterion in the diagnosis and differentiation of the different types of nerve sheath tumors.”

Press contacts:
Dr. Friederike Fellenberg
Nationales Centrum für Tumorerkrankungen (NCT) Heidelberg
Presse- und Öffentlichkeitsarbeit
Im Neuenheimer Feld 460
69120 Heidelberg
Tel.: +49 6221 56-5930
Fax: +49 6221 56-5350
E-Mail: friederike.fellenberg@nct-heidelberg.de

Doris Rübsam-Brodkorb
Universitätsklinikum Heidelberg und Medizinische Fakultät der Universität Heidelberg
Presse- und Öffentlichkeitsarbeit
Im Neuenheimer Feld 672
69120 Heidelberg
Tel.: +49 6221 56-5052
Fax: +49 6221 56-4544
E-Mail: doris.ruebsam-brodkorb@med.uni-heidelberg.de

Dr. Sibylle Kohlstädt
Deutsches Krebsforschungszentrum (DKFZ)
Presse- und Öffentlichkeitsarbeit
Deutsches Krebsforschungszentrum
Im Neuenheimer Feld 280
69120 Heidelberg
Tel.: +49 6221 42-2843
Fax: +49 6221 42-2968
E-Mail: s.kohlstaedt@dkfz.de

The National Center for Tumor Diseases (NCT) Heidelberg
The National Center for Tumor Diseases (NCT) Heidelberg is a joint institution of the German Cancer Research Center, Heidelberg University Hospital and German Cancer Aid. The NCT's goal is to link promising approaches from cancer research with patient care from diagnosis to treatment, aftercare and prevention. The interdisciplinary tumor outpatient clinic is the central element of the NCT. Here the patients benefit from an individual treatment plan prepared in a timely manner in interdisciplinary expert rounds, the so-called tumor boards. Participation in clinical studies provides access to innovative therapies. The NCT thereby acts as a pioneering platform that translates novel research results from the laboratory into clinical practice. The NCT cooperates with self-help groups and supports them in their work. 2015 the NCT Heidelberg established a partner location in Dresden.

The German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ)
The German Cancer Research Center (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.

Heidelberg University Hospital and Medical Faculty Heidelberg
Heidelberg University Hospital is one of the most important medical centers in Germany; Heidelberg University's Medical Faculty is one of Europe's most prestigious biomedical research facilities. Their shared objective is the development of innovative diagnostics and treatments and their prompt implementation for the benefit of the patient. The hospital and faculty employ approximately 12 600 individuals and are involved in training and qualification. Every year approximately 66 000 patients are treated as inpatients or day patients in more than 50 specialized clinical departments with about 1 900 beds, with more than 1 million patients being treated as outpatients. The Heidelberg Curriculum Medicinale (HeiCuMed) is at the forefront of medical training in Germany. At present approx. 3500 prospective physicians are studying in Heidelberg.