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Protein Overexpression Tied to Pancreatic Cancer

December 16, 2019

A preclinical study led by researchers at The University of Kansas Cancer Center has identified a potential new target in the treatment of pancreatic ductal adenocarcinoma, the most common type of pancreatic cancer. Their findings were published in Gastroenterology.

According to principal investigator Animesh Dhar, PhD, a protein called histone lysine demethylase 3A (KDM3A), plays a role in pancreatic cancer tumor development and regulates DCLK1, a well-known pancreatic cancer stem cell marker. “We have found reducing KDM3A in pancreatic cancer cells significantly reduces malignant properties and slows growth of tumors in mice,” Dr. Dhar said. “In contrast, overexpression of KDM3A causes significant tumor growth.”

Another piece of the puzzle

Pancreatic cancer cells thrive in low oxygen through the increased presence of hypoxia-inducible factor (HIF)-1, a protein structure that supports our body's response to low oxygen supply at the tissue level. HIF-1 is one of the primary genes that can increase vascularization by forming new blood vessels, and it is tied to cancer growth because it provides nutrients and oxygen for tumors to flourish.

In addition to discovering human pancreatic cancer samples and cell lines overexpress KDM3A, Dr. Dhar and his team have also found hypoxia increases expression of KDM3A in pancreatic cancer cells.

“This study builds on our understanding of KDM3A’s role in the regulation of DCLK1. Future treatments may be able to disrupt the connection between hypoxia and KDM3A.” Dr. Dhar said. “Pancreatic ductal adenocarcinoma is the fourth leading cause of cancer-related mortality in the United States, due to its susceptibility to metastasis. We are working urgently to find a better treatment to improve survival.”

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