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Study a 'stepping stone' in pancreatic cancer battle

Image with caption: From left, Moorthy Ponnusamy, PhD, and Surinder Batra, PhD

From left, Moorthy Ponnusamy, PhD, and Surinder Batra, PhD

Surinder Batra, PhD, chairperson and Stokes-Shackelford Professor in the UNMC Department of Biochemistry and Molecular Biology, and Moorthy Ponnusamy, PhD, associate professor in biochemistry and molecular biology, recently published a study revealing how a small population of pancreatic cancer cells with stem cell-like features is responsible for the disease aggressiveness, metastasis, recurrence and drug resistance.

Pancreatic cancer is the third-leading cause of cancer-related death in the United States, with an estimated 47,000 people dying from the disease this year alone.

Much about the pathogenesis of pancreatic cancer is related to the fact that it is difficult to diagnose and is often found in later stages when it can no longer be surgically removed or has spread to other parts of the body.

Dr. Batra has spent decades decoding this complex disease, while Dr. Ponnusamy's work has focused on pancreatic cancer stem cells.

Drs. Batra and Ponnusamy's latest findings were published in the August issue of the journal Gastroenterology.

"This subset of cancer cells with tumor-initiating potential are called cancer stem cells," Dr. Batra said. "Yet, conventional therapies are directed at tumor cells instead of targeting the cancer stem cell population."

Drs. Batra and Ponnusamy's team found that cancer stem cell features in pancreatic cancer are maintained by a biomolecule known as PAF1. PAF1 - a naturally occurring ribonucleic acid (RNA) polymerase II-associated factor 1 complex component -- actually contributed to the development of pancreatic cancer tumors at an alarming rate.

The question then became, could PAF1 be stopped and, if so, would it impact the exponential growth that pancreatic cancer tumors are known for?

The team discovered, using mice models, that it is possible to downregulate PAF1 and interrupt the cycle of growth and stem cell maintenance needed to continue that growth in pancreatic cancer stem cells, thus inhibiting the overall growth of the tumor.

"This study serves as a stepping-stone for targeting PAF1-dependent pancreatic cancer stem cells and we hope presents a therapeutic window to target," Dr. Batra said.

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