Gene Linked to Pancreatic Cancer Growth

A mutant protein found in nearly all pancreatic cancers plays a role not only in the cancer’s development but in its continued growth, according to a new study from University of Michigan Comprehensive Cancer Center researchers. The finding suggests a possible target for developing new ways to treat this deadly disease.

Researchers have known that mutations in the Kras gene are what cause pancreatic cancer to develop. These mutations are frequently seen in common precancerous lesions, suggesting it has an early role in pancreatic cancer.

The new study, published in the February Journal of Clinical Investigation, finds that in mice, mutant Kras also keeps the tumor growing and helps precancerous tumors grow into invasive cancer. When the researchers turned off Kras, the tumors disappeared and showed no signs of recurring.

The researchers were able to manipulate Kras in a mouse model that they designed to look at Kras at various points in pancreatic cancer development. In the precancerous lesions, turning off Kras eliminated the tumors in mice and the pancreas tissue returned to normal, with no signs of the cancer returning. With invasive cancer, inactivating Kras killed off the cancer but left the pancreas with fibrous areas similar to scar tissue. Tumors did not recur.

Researchers hope this finding provides the basis for future drug development.

“Right now no drugs specifically target Kras, but there are drugs that target the cellular processes downstream of Kras. We next need to figure out which of these downstream effectors of Kras are important in pancreatic cancer,” says study author Marina Pasca di Magliano, Ph.D., assistant professor of surgery and of cell and developmental biology at the U-M Medical School.

Gene Involved In Pancreatic Cancer Identified Researchers from the University of Michigan Comprehensive Cancer Center have identified a gene that is overexpressed in 90 percent of pancreatic cancers, the most deadly type of cancer.

Expression of the gene, Ataxia Telangiectasia Group D Complementing gene, called ATDC, is on average 20 times higher in pancreatic cancer cells than in cells from a normal pancreas. What’s more, the gene appears to make pancreatic cancer cells resistant to current therapies.

“One of the challenges in pancreatic cancer is that it is biologically aggressive and it does not respond well to chemotherapy or radiation. We found that ATDC not only causes the cancer cells to grow faster and be more aggressive, but it also makes the cancer cells particularly resistant to chemotherapy and radiation. By targeting this gene, we may be able to make cancer cells more sensitive to the therapies we already have in hand,” says senior study author Diane Simeone, M.D., director of the Multidisciplinary Pancreatic Cancer Clinic at the U-M Comprehensive Cancer Center.

Results of the study appear in the March issue of Cancer Cell.