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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

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:

  • National Center for Tumor Diseases (NCT, 6 sites)
  • German Cancer Consortium (DKTK, 8 sites)
  • Hopp Children's Cancer Center (KiTZ) Heidelberg
  • Helmholtz Institute for Translational Oncology (HI-TRON Mainz) - A Helmholtz Institute of the DKFZ
  • DKFZ-Hector Cancer Institute at the University Medical Center Mannheim
  • National Cancer Prevention Center (jointly with German Cancer Aid)
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.


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