Cancer Center Members Find New Drug Target for Pancreatic Cancer

University of Illinois Cancer Center researchers have discovered a potential drug target for treating aggressive pancreatic cancer.

Their findings, detailed in Oncogene, showed that an experimental compound inhibited pancreatic cancer in mice, significantly extending their survival and reducing tumor growth in a mouse model of pancreatic ductal adenocarcinoma.

The data showed that the proteins MLK3 and MAP4K4 are overexpressed in pancreatic cancer cell lines and tumors. The research team was led by Endowed Professor Ajay Rana, PhD, director of research, and the first author, Sunil K. Singh, PhD, from the Department of Surgery at the University of Illinois at Chicago College of Medicine.

Building on the lab’s previous findings, the team planned to clarify the functions of the MAP4K4-MLK3 axis in pancreatic cancer models, according to Rana and Singh.

“Interestingly, the MAP4K4 expression positively correlates with pancreatic tumor grades and higher expression leads to a worse prognosis for patients. Inhibiting MAP4K4 signaling in pancreatic cancer cell lines often caused the cancer cell to undergo programmed cell death,” Rana explained. “This extended survival in mice with aggressive disease and points to a potential therapy for patients with pancreatic cancer.”

It’s important to note that the novel compound used in the study is not currently approved for human consumption. The compound, known as GNE-495, induced cancer cell death, blocked cell cycle progression, and prevented migration of pancreatic cancer cells in the study. In addition to lessening the tumor burden, mice treated with GNE-495 showed a reduced tumor grade and fewer malignant ducts.

Pancreatic cancer is associated with abnormal inflammatory cell processes. Adenocarcinoma is the most common type of pancreatic cancer, accounting for more than 90% of pancreatic cancer diagnoses. It is typically detected at a late stage, resulting in low five-year survival rates.

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