Navigation Links
UC Davis researchers discover Achilles' heel in pancreatic cancer

UC Davis Cancer Center researchers have discovered a metabolic deficiency in pancreatic cancer cells that can be used to slow the progress of the deadliest of all cancers.

Published in the October issue of the International Journal of Cancer, study results indicate that pancreatic cancer cells cannot produce the amino acid arginine, which plays an essential role in cell division, immune function and hormone regulation. By depleting arginine levels in cell cultures and animal models, the team was able to significantly reduce pancreatic cancer-cell proliferation.

"There have been few significant advances in 15 years of testing available chemotherapy to treat pancreatic cancer," said Richard Bold, chief of surgical oncology at UC Davis and senior author of the study. "The lack of progress is particularly frustrating because most patients are diagnosed after the disease has spread to other organs, eliminating surgery as an option. We have to turn back to basic science to come up with new treatments."

Bold explained that average survival time for those diagnosed with pancreatic cancer is just four-and-a-half months, although chemotherapy can extend that prognosis up to six months.

"There is a dire need to find new options for these patients. While our findings do not suggest a cure for pancreatic cancer, they do promise a possible way to extend the life expectancies of those diagnosed with it," Bold said.

Bold and his colleagues hypothesized that pancreatic cancer cells lack the ability to produce arginine. In human pancreatic tumors, they measured levels of an enzyme argininosuccinate synthetase required to synthesize arginine.

The enzyme was not detected in 87 percent of the 47 tumor specimens examined, suggesting that the majority of pancreatic cancers require arginine for cell growth because of an inability to synthesize the amino acid.

The researchers then conducted further tests using pancreatic cell lines that represent the varying levels of argininosuccinate synthetase observed in human tumor specimens. Focusing on the lines with lowest levels, the researchers depleted arginine levels in cultures of pancreatic cell lines using arginine deiminase, an enzyme isolated from a Mycoplasma bacteria.

The enzyme was modified by adding polyethylene glycol chains to increase size and circulatory time.

The researchers found that exposing the pancreatic cancer cell lines to the modified arginine deiminase enzyme inhibited cancer-cell proliferation by 50 percent. They then treated mice bearing pancreatic tumors with the same compound and found an identical outcome: a 50 percent reduction in tumor growth. According to Bold, the current study represents a unique approach to cancer treatment in that it is one of the first to identify a metabolic pathway that can be leveraged to interrupt cancer growth.

"Instead of killing cells as with typical chemotherapy, we instead removed one of the key building blocks that cancer cells need to function," Bold said.

Metabolic interruptions like this one are also being studied for their potential in treating cancers of the blood, such as leukemia and lymphoma. In those cases, depleting the amino acid asparagine may be used in slowing cancer-cell growth.

Bold and his colleagues are continuing their laboratory work on the effects of arginine deprivation on pancreatic cancer. They will next be looking for ways to increase pancreatic cell sensitivity to arginine deprivation.

The researchers have also begun designing human clinical trials in cooperation with the manufacturer of arginine deiminase, Polaris Pharmaceuticals.

"We're looking at whether we can combine this treatment with certain kinds of chemotherapy," Bold said. "This additional research is needed to inform the clinical work and move it forward more quickly. The better we understand this process, the more we can use it in the fight against pancreatic cancer."


Contact: Karen Finney
University of California - Davis - Health System

Related biology news :

1. UC Davis researchers discover a key to aggressive breast cancer
2. UC Davis chemical ecologist wins major award
3. UC Davis researchers discover new drug target for inflammatory disease
4. UC Davis researchers define characteristics, treatment options for XXYY syndrome
5. UC Davis researcher leads climate-change discovery
6. UC Davis stem researchers demonstrate safety of gene therapy using adult stem cells
7. UC Davis researchers discover how HIV turns food-poisoning into lethal infection
8. UC Davis bird-flu expert calls for changes in early-warning system
9. Repairing DNA damage: Researchers discover critical process in cancer treatment
10. Corn researchers discover novel gene shut-off mechanisms
11. Researchers at UH explore patient preferences for personalized medicine
Post Your Comments:
(Date:4/26/2016)... and LONDON , ... Finacle, part of EdgeVerve Systems, a product subsidiary ... Onegini today announced a partnership to integrate the ...      (Logo: ) ... provide their customers enhanced security to access and ...
(Date:4/15/2016)... , April 15, 2016  A new partnership ... more accurate underwriting decisions in a fraction of ... competitively priced and high-value life insurance policies to ... With Force Diagnostics, rapid testing (A1C, ... data readings (blood pressure, weight, pulse, BMI, and ...
(Date:4/13/2016)... April 13, 2016  IMPOWER physicians supporting Medicaid patients ... a new clinical standard in telehealth thanks to a ... the higi platform, IMPOWER patients can routinely track key ... body mass index, and, when they opt in, share ... visit to a local retail location at no cost. ...
Breaking Biology News(10 mins):
(Date:6/27/2016)... ... June 27, 2016 , ... Parallel 6 , the leading software as ... Clinical Reach Virtual Patient Encounter CONSULT module which enables both audio and video ... trial team. , Using the CONSULT module, patients and physicians can schedule a face ...
(Date:6/27/2016)... , June 27, 2016   Ginkgo Bioworks ... to industrial engineering, was today awarded as one ... selection of the world,s most innovative companies. Ginkgo ... scale for the real world in the nutrition, ... engineers work directly with customers including Fortune 500 ...
(Date:6/24/2016)... ... ... Researchers at the Universita Politecnica delle Marche in Ancona combed medical journal ... Their findings are the subject of a new article on the Surviving Mesothelioma website. ... the blood, lung fluid or tissue of mesothelioma patients that can help point doctors ...
(Date:6/23/2016)... - FACIT has announced the creation of a ... Propellon Therapeutics Inc. ("Propellon" or "the Company"), to ... of first-in-class WDR5 inhibitors for the treatment of ... an exciting class of therapies, possessing the potential ... patients. Substantial advances have been achieved with the ...
Breaking Biology Technology: