Pancreatic Cancer Treatment

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Brandi Klingerman | September 26, 2017

New Notre Dame research has been used to support the Orphan Drug designation for IT-139, a compound that when used in combination with chemotherapy has proved to be significantly more effective in treating pancreatic cancer than the current standard of care. The Orphan Drug program is administered by the Food and Drug Administration (FDA) and identifies promising drugs that are intended for the treatment of rare diseases, which impact fewer than 200,000 Americans at any time, or affect more than 200,000 people but are not expected to recover the costs of developing and marketing a treatment drug. Currently, pancreatic cancer has one of the lowest cancer survival rates, with one-year and five-year rates of 20 and 7 percent, respectfully. 

In the study, Reginald Hill, the Archibald Assistant Professor of Cancer Biology and affiliated faculty member of the Harper Cancer Research Institute, and his lab investigated how a pancreatic tumor’s microenvironment affects a pancreatic cancer tumor’s chemotherapy resistance. A hallmark of this disease is that inflammation causes the cancer cells to produce an increased amount of misfolded proteins, or proteins that have not been properly processed by the cancer cells. The Notre Dame researchers saw that when this happened, pancreatic cancer cells increased production of GRP78, a protein that helps cells that have not been properly processed survive. 

In explanation, Hill said, “GRP78 is a chaperone protein, or a protein that is expressed by cells to help them survive stressful conditions that would otherwise lead to cell death, such as an accumulation of misfolded proteins. We theorized that without the chaperone protein, the abundance of misfolded proteins would inhibit the cancer cell’s ability to thrive.”

To test the idea, Hill’s lab utilized IT-139, a GRP78 protein induction inhibitor, to reduce expression of the chaperone protein in pancreatic cancer cells. In turn, the Notre Dame researchers found that in initial tests, the cells with inhibited GRP78 production had become significantly more susceptible to chemotherapy. These initial results were further confirmed with additional models containing pancreatic tumor cells.

Read more here.

 by Daily Domer Staff

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