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UCSD Study: New Therapy May Increase Pancreatic Cancer Survival Rate

Bare branches sit in the foreground of the UC San Diego's Moores Cancer Cente...

Photo by Tarryn Mento

Above: Bare branches sit in the foreground of the UC San Diego's Moores Cancer Center, Jan. 16, 2020.

Researchers at the UC San Diego School of Medicine and Moores Cancer Center were among the lead scientists in a study, released Tuesday, which concluded that a new tumor-penetrating therapy, tested in animal models, may enhance the effects of chemotherapy, reduce metastasis and increase survival from pancreatic cancer.

Every 12 minutes, someone in the United States dies of pancreatic cancer, which is often diagnosed late, spreads rapidly and has a five-year survival rate of around 10%. Treatment may involve radiation, surgery and chemotherapy, though often the cancer becomes resistant to drugs.

The study, published online in Nature Communications, showed how a tumor-targeting peptide, called iRGD, can sneak inside the armor that the tumor built to protect itself and use the fibrous tissue as a highway to reach deeper inside, destroying the tumor from within. The study was conducted in collaboration with Sanford-Burnham-Prebys Medical Discovery Institute and Columbia University.

The pancreas is a large gland located behind the stomach. It makes enzymes that aid digestion and hormones that regulate blood-sugar levels. Pancreatic ductal adenocarcinoma is a subtype of pancreatic cancer that is highly drug-resistant due, in part, by the hard shell-like outer layer surrounding the tumor.

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"This type of tumor is made up of a dense fibrous tissue that acts as a barrier to drugs trying to get through," said Tatiana Hurtado de Mendoza, an assistant project scientist at UCSD School of Medicine and Moores Cancer Center and first author of the study.

"Many drugs can reach the vessels of the tumor, but they are not able to get deep into the tissue, making treatment less effective, and that is one reason why this type of cancer is so challenging to treat," she said. "Our study found that the tumor-penetrating peptide iRGD is able to use this fibrous network to deliver chemotherapy drugs deep into the tumor and be more effective."

The research team examined the microenvironment of the tumors in a mouse model. They found that after targeting the tumor blood vessels, the peptide binds to high levels of a protein produced by cells that produce much of the tumor's protective fibrous cover.

"This could be a powerful treatment strategy to target aggressive pancreatic cancer," said Dr. Andrew Lowy, co-corresponding author of the study.

"What is also exciting about this finding is the iRGD therapy did not produce any additional side effects. This is critically important when considering treatments for patients," said Lowy, a professor of surgery at the UCSD School of Medicine and chief of the Division of Surgical Oncology at Moores Cancer Center at UCSD Health.

The researchers said next steps include a national human clinical trial. They estimate the trial could begin in one year.

"The knowledge gained from our study has the potential to be directly applied to patient care," Lowy said.

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