Press and Public Relations

Rare pancreatic cancer reveals targets for therapy

No. 53c | 06/11/2017 | by Koh

Scientists from the German Cancer Research Center (DKFZ) have conducted comprehensive molecular analyses of a rare type of pancreatic cancer. They have discovered a variety of cellular alterations that can be targeted by drugs that are already available and in part even already approved for therapy.

© Wellcome Library, London

Malignant growths in the pancreas are still considered among the cancer types with the poorest prognosis; barely ten percent of affected patients survive the first five years after diagnosis. Physicians and researchers are therefore urgently trying to find targeted new methods to combat the disease.

Approximately 90 percent of pancreatic cancers start in the ducts of the pancreas. In addition, there are a number of much less common cancer types, including acinar cell carcinoma, that develop from specific exocrine cells of the pancreas. Since this type of cancer is extremely rare and accounts for only about two percent of all cases of pancreatic cancer, very little is known about this disease.

Scientists think that the various types of pancreatic cancer differ considerably in their tumor biology. In order to be able to use targeted drugs for precision attacks on the cancer-driving cellular alterations, the molecular characteristics of each of these groups of tumors must first be known. A team led by Peter Schmezer, Odilia Popanda and Christoph Plass from the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ), in collaboration with colleagues from the Pathology Institute of Heidelberg University Hospital, has now conducted the world's largest study on this rare disease. The investigators performed comprehensive molecular analyses of tissue samples from 74 cases of acinar cell carcinoma.

In their analysis of acinar cell carcinomas, the DKFZ researchers found no recurrent cancer-promoting point mutations in tumor-relevant genes, which are characteristic for pancreatic ductal carcinomas. Instead, these tumors are characterized by deletion or amplification of genetic material, sometimes affecting extended sections of the genome. Very frequently, the labeling of the genome with small chemical labels differs from methylation patterns in healthy cells. This so-called epigenetic code determines which genes are transcribed or stay silent, thus having a crucial impact on cancer development and spread.

In approximately 70 percent of the acinar cell carcinomas under investigation, the researchers discovered defective DNA repair genes that can result in the failure of cells to repair defects in the genetic material. In addition, the investigators found frequent mutations in genes that control the cell cycle as well as genetic defects that are caused by tobacco consumption.

"The results confirm that acinar cell carcinoma of the pancreas has a completely different tumor biology and, hence, a different development history than tumors of the pancreatic duct," Schmezer said. "The good news is that for many of the frequent alterations that we found in acinar cell carcinoma, targeted agents are already available and some of them are even already approved for therapy."

For very rare cancers such as acinar cell carcinoma of the pancreas, it is difficult to test the effectiveness of novel drugs in classic clinical trials. A new concept called basket trial may now solve this problem. Rather than focusing on a particular cancer type, basket trials test therapies in patients whose tumors exhibit identical cancer-promoting genetic mutations, regardless of where the cancer originated.

Cornelia Jäkel, Frank Bergmann, Reka Toth, Yassen Assenov, Daniel van der Duin, Oliver Strobel, Thomas Hank, Günter Klöppel, Craig Dorrell, Markus Grompe, Joshua Moss, Yuval Dor, Peter Schirmacher, Christoph Plass, Odilia Popanda, Peter Schmezer: Genome-wide genetic and epigenetic analyses of pancreatic acinar cell carcinomas reveal aberrations in genome stability

Nature Communication 2017, DOI: 10.1038/s41467-017-01118-x

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