Pancreatic cancer carries one of the highest mortality rates of any cancer worldwide. One reason for this is that the disease is inexplicably aggressive. It metastasizes early. New research, however, by teams from Germany points towards an explanation. Keep reading to learn more about this discovery, or follow the original story here.
No previous research determined how pancreatic cancer moves so quickly. Nothing seemed to connect the aggressive behavior and mutations of the disease to its genome. That is, until a German team, comprised of researchers from the Technical University of Munich (TUM), and the German Cancer Consortium (DKTK) found a connection. Using an assortment of mouse models, the researchers shed light on the molecular pathways the disease follows as it develops.
Part of their discovery lies in the number of gene copies cancer cells have.
Human cells, when healthy, hold two copies of every gene. During their studies, researchers manipulated a gene in mice (KRAS) which is found active in 90% of all human pancreatic tumoxxrs. Surprisingly, researchers discovered the gene created copies of itself early on. In cases where tumors did not replicate the mutated gene, researchers discovered copies in other genes related to cancer.
“It therefore appears that the cell amplifies the growth signal due to the presence of extra gene copies,” says lead author Sebastian Müller. “This model of dosage amplification during tumor development had not previously been considered.”
Researchers were also able to link the number of copied KRAS genes to how aggressive and readily metastasized tumors were.
Another finding connected pancreatic cancer development to impairment of protective genes. Tumor suppressor genes protect healthy cells. Introduction of KRAS mutation, however, triggered mutations in these protector genes. Researchers discovered that KRAS, or other cancer genes, are amplified depending on the type of suppressor gene that is affected. The degree to which the suppressor gene is incapacitated also plays a role.
The research conducted in this study also explains the various stages of development pancreatic cancer follows.
Researchers noted that tumors are only able to form after a cells protective measures are disabled. In addition, dosage amplification is necessary for a tumor to form. In other words, a cell must be weakened, and the number of mutated genetic copies must increase. By tracing the genes involved, a path for the cell can be determined, and the qualities of the tumor predicted.
“We have indications that our discovery constitutes a fundamental principle in the development of tumors and plays an essential role in other cancers,” explains professor Roland Rad. “We’re now investigating the extent to which these new insights into cancer biology can be used to develop new therapeutic strategies.”