Joint press release by NCT Heidelberg and NCT Dresden
The discovery of growth-enhancing gene fusions in tumors of the pancreas paves the way for new approaches for targeted therapies – as scientists at the National Center for Tumor Diseases in Dresden (NCT) and the NCT Heidelberg have discovered. Patients whose tumors show this specific change may benefit from the use of certain medications.
Tumors of the pancreas are particularly aggressive and difficult to treat. About 18,500 people develop this type of cancer in Germany every year. Mutations in the so-called KRAS gene, which cause the tumor cells to divide incessantly, are among the most common genetic alterations in pancreatic cancer. However, not every tumor of the pancreas develops this mutation. If the KRAS gene remains the same, other changes to the genetic information often play an important role. Scientists at the National Center for Tumor Diseases (NCT) were able to reveal this connection. In several cases, they discovered what they called gene fusions: A portion of a specific gene, the so called NRG1 gene, was fused with the part of another gene. Unlike KRAS mutations, cancer cells containing such merged genes are vulnerable to certain medications.
This was examined in close cooperation between physicians and scientists at the two NCT sites in Heidelberg and Dresden based on detailed molecular analysis of a group of young patients. The NCT is a cross-site collaboration of the German Cancer Research Center (DKFZ) and the Heidelberg University Hospital (HUH) on the one hand and the DKFZ and the Dresden University Hospital, the Medical Faculty of the Technical University of Dresden and the Dresden-Rossendorf Helmholtz Center (HZDR) on the other hand. Deciphering the genetic code of the tumors by DNA and RNA sequencing was carried out in the German NCT/DKTK MASTER (Molecularly Aided Stratification for Tumor Eradication Research) program.
“We observed a different genetic peculiarity instead of KRAS mutations in four of the 17 patients studied: we found certain gene sections that were fused with others,” explains Hanno Glimm, Managing Director at the NCT in Dresden and Head of the Department for “Translational Medical Oncology”. Gene mergers lead to tumor growth whenever a normally strictly regulated healthy gene merges with another gene section that is particularly active, and thus repeals any regulation.
“Tumors of the pancreas with KRAS mutations hardly respond to drugs. However, cancer cells with these specific gene fusions can be treated with approved agents, so-called tyrosine kinase inhibitors or even antibodies. This gives us more options for treating these patients,” explains Stefan Fröhling, Managing Director at the NCT Heidelberg. Two of the patients were given specific drugs for treating the genetic changes. In both patients, liver metastases temporarily receded at a time when other therapies were no longer able to control the disease.
“We were thus able to show that it makes sense to treat pancreatic cancer patients with treatments tailored to the individual characteristics of the tumor,” says Christoph Heining of the NCT Dresden. What the ideal treatment with specific drugs might look like will be the focus of an additional study at the NCT’s two sites. In the interests of selecting suitable patients for personalized therapy, the scientists propose a two-stage process of diagnosis: Initially, the patients should be tested for whether their tumors have the non-mutated form of the KRAS gene. If this is the case, clinically vulnerable genetic mergers will be determined in a following step.
For their study, the scientists specifically chose a group of young patients aged between 24 and 49 years. There is little data on the genetic foundations of pancreatic cancer for this age group, since these tumors are mostly diagnosed in men and women 65 years and older. However, comparative analyses of existing data material indicate that genetic mergers are likely to also play an important role in older patients.
Heining, P. Horak, S. Uhrig et al. (2018) NRG1 Fusions in KRAS Wild-type Pancreatic Cancer. Cancer Discovery DOIxxxx
Press contact:
Dr. Friederike Fellenberg
National Center for Tumor Diseases Heidelberg (NCT)
Press and public relations
Im Neuenheimer Feld 460
69120 Heidelberg
Tel.: +49 6221 56-5930
Fax: +49 6221 56-5350
Email: friederike.fellenberg@nct-heidelberg.de
www.nct-heidelberg.de
Dr. Anna Kraft
National Center for Tumor Diseases Dresden (NCT)
Press and public relations
Fetscherstraße 74/PF 41
01307 Dresden
Tel.: +49 (0)351 458-7440
Email: anna.kraft@nct-dresden.de
www.nct-dresden.de
National Center for Tumor Diseases Heidelberg (NCT)
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. This is true for both diagnosis and treatment, follow-up care or 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. In 2015, the NCT Heidelberg established a partner location in Dresden.
National Center for Tumor Diseases Dresden (NCT)
In addition to Heidelberg, the National Center for Tumor Diseases (NCT) has maintained a second site in Dresden since 2015. The NCT Dresden is a joint institution of the German Cancer Research Center (DKFZ), Carl Gustav Carus University Hospital in Dresden, the Medical Faculty of the Technical University of Dresden and the Dresden-Rossendorf Helmholtz Center. The NCT is committed to the task of linking research and patient care as closely as possible. Thus, cancer patients in Dresden and Heidelberg can be treated with the latest state-of-the-art treatments. At the same time, scientists at the NCT benefit in their practical research from the proximity between the laboratories and clinics. A common goal of both sites is to develop the NCT into an international center of excellence in cancer research. After successful completion of the set-up phase, the annual endowment of NCT Dresden will be 15 million euros starting in 2019. This amount is funded by a ratio of 90 to 10 percent by the German Federal Government and Free State of Saxony. The Free State of Saxony has provided an additional 22 million euros for the construction of the new NCT building.