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Tuesday, October 19, 2021

UC Davis researchers discover metabolic deficiency in pancreatic cancer cells

In an effort to develop new cancer treatments, UC Davis Cancer Center researchers might have struck gold.

Researchers have discovered a metabolic deficiency in pancreatic cancer cells that could potentially be used as a treatment for pancreatic cancer.

Led by Chief of Surgical Oncology at UC Davis Richard Bold, the findings reveal that pancreatic cancer cells lack the ability to create the amino acid arginine, which plays an important role in cell division. By monitoring and decreasing the levels of arginine present in the cells, Bold and his team were able to drastically reduce the production of pancreatic cells.

“We tested the cells for the presence of an enzyme in the biosynthetic pathway,Bold said in an e-mail interview.Some other cancers also lack this enzyme so we hypothesized that pancreatic cancer would as well.

Bold and his colleagues measured the levels of a specific enzyme argininosuccinate synthetasein human pancreatic tumors, which is necessary for synthesizing arginine. The enzyme was not found in 87 percent of tumors examined, providing evidence that the majority of the pancreatic tumors need arginine present in the cell for cell growth since it is not able to make the amino acid itself.

The next step required the researchers to deplete the levels of arginine in cancer cells using another enzymearginine deiminasethat was modified to be used in the study. The results showed a decrease of cancer cell growth by 50 percent. Similar results were observed when mice with pancreatic tumors were treated with the modified enzyme.

According to the National Cancer Institute’s website, approximately 37,680 new cases of pancreatic cancer developed in 2008 as well as 34,290 deaths due to the disease. It usually cannot be detected in earlier stages because its symptoms are similar to other illnesses.

Current treatments for pancreatic cancer include surgery, radiation therapy and chemotherapy, according to the National Cancer Institute’s website. If the size of the malignant tumor is too large or if the cancer has spread to other parts of the body, surgery cannot be done to remove it but only to relieve symptoms.

Radiation therapy involves using high-energy X-rays or other radiation to kill cancer cells or prevent them from growing.

Lastly, chemotherapy uses drugs to either kill or stop cancer cells from growing. Usually a combination of these methods is used for treatment, but their effectiveness is limited.

“[This finding] is very important for pancreatic cancer, since our current treatment doesn’t work very well,Bold said.

The next step for the study is a clinical trial of the modified enzyme in the early part of 2009, Bold said. The scientists will continue research to find out why all cells don’t respond to the enzyme and whether the pancreatic cancer cells may become resistant to the therapy.

“A clinical trial with arginine deiminase for pancreatic cancer patients is in the early planning stages,said Randie Kim, a UC Davis graduate student and one of the authors of the study in an e-mail.Our eventual hope is that [this enzyme] can be combined with other chemotherapies for a one-two punch against pancreatic cancer.

In addition to pancreatic cancer, arginine deiminase has been shown to be effective in other cancers, including prostate cancer, liver cancer, hepatocellular carcinomas and melanomas, Kim said. Clinical trials for patients in early phase I and phase II of advanced hepatocellular carcinomas and melanomas have already occurred with encouraging results.

But despite all the apparent success of the study, Kim concluded that their work is not over just yet.

“There is still a lot of research to be done,Kim said.

 

NICK MARKWITH can be reached at campus@theaggie.org 

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