Scientists find potential loophole in pancreatic cancer defenses

March 27, 2013 by Richard Saltus

Dana-Farber Cancer Institute scientists and colleagues have discovered that pancreatic cancer cells' growth and spread are fueled by an unusual metabolic pathway that someday might be blocked with targeted drugs to control the deadly cancer.

Cancer cells are known to "rewire" their metabolic circuits differently from normal cells to provide energy for cancerous growth. A study published today in Nature reveals that pancreatic are dependent on an amino acid, glutamine, which they utilize via a molecular pathway that has no apparent backup system.

"Pancreatic cancer cells have painted themselves into a metabolic bottleneck," said Dana-Farber's Alec Kimmelman, MD, PhD, co-senior author of the publication with Lewis Cantley, PhD, of Weill Cornell Medical College. Their research showed "that if you suppress any enzyme in that pathway, the cancer cells cannot effectively compensate and they can no longer grow," Kimmelman said.

Moreover, the investigators said, this novel glutamine pathway in pancreatic tumors does not appear to be important for normal cells, suggesting that inhibitor drugs could block cancer cells' growth without harming healthy tissues and organs.

"We don't have a drug to do this in humans," Kimmelman said, "but we are working on inhibitors of enzymes in the glutamine pathway."

The research showed that the cancer gene KRAS, which is the "signature" genetic mutation occurring in pancreatic cancer, directs the metabolic rewiring that creates the tumors' dependence on the glutamine pathway. KRAS, Kimmelman explained, changes the expression of key enzymes that maintain this pathway.

Pancreatic cancer is one of the most lethal and treatment-resistant of all cancers, with a dismal survival rate, and scientists have been searching for any vulnerability that could be exploited. One of the newer strategies in cancer research is studying the between cancer cells and normal cells with the goal of depriving tumors of their fuel.

In order to grow, cells must prevent the accumulation of damaging oxygen "free radicals," and they do so by maintaining a chemical "redox balance." The researchers found that when they blocked any of several enzyme reactions in the glutamine pathway, it undermined redox balance and suppressed the growth of human pancreatic cancer cells transplanted to mice.

If drugs can be developed to shut down the glutamine pathway, Kimmelman suggested, they might make more susceptible to standard treatments, such as radiation and chemotherapy, that cause free radicals to accumulate in .

Explore further: Advanced pancreatic tumors depend on continued oncogene activity

Related Stories

Advanced pancreatic tumors depend on continued oncogene activity

April 26, 2012
Researchers at Dana-Farber Cancer Institute have shown that advanced pancreatic cancers in mice can't survive without continued expression of a mutant oncogene that "rewires" key metabolic pathways to fuel the cancer cells.

Scientists find new molecule to target in pancreatic cancer treatment

January 3, 2013
Researchers at Mayo Clinic in Florida have identified a new target to improve treatment of pancreatic ductal adenocarcinoma cancer, which accounts for more than 95 percent of pancreatic cancer cases. This fast-growing, often ...

Embryonic signal drives pancreatic cancer and offers a way to kill it

November 3, 2011
Pancreatic cancer is a particularly challenging one to beat; it has a tendency to spread and harbors cancer stem cells that stubbornly resist conventional approaches to therapy. Now, researchers reporting in the November ...

Chemo may get boost from cholesterol-related drug

April 3, 2012
Johns Hopkins investigators are testing a way to use drugs that target a cholesterol pathway to enhance the cancer-killing potential of standard chemotherapy drugs. Their tests, in mouse models of pancreatic cancer, may yield ...

Inhibiting Hedgehog signaling pathway may improve pancreatic cancer treatment

June 19, 2012
Combining a new targeted therapy with standard chemotherapy may help defeat pancreatic cancer, according to results presented at the American Association for Cancer Research's Pancreatic Cancer: Progress and Challenges conference, ...

Nerve growth factors elevated in pancreatic cancer model

June 19, 2012
Severe pain is a major symptom of pancreatic cancer. The results of a new study show that four different factors involved in the growth and maintenance of nerves are elevated in a mouse model of pancreatic cancer. This is ...

Recommended for you

No dye: Cancer patients' gray hair darkened on immune drugs

July 21, 2017
Cancer patients' gray hair unexpectedly turned youthfully dark while taking novel drugs, and it has doctors scratching their heads.

Shooting the achilles heel of nervous system cancers

July 20, 2017
Virtually all cancer treatments used today also damage normal cells, causing the toxic side effects associated with cancer treatment. A cooperative research team led by researchers at Dartmouth's Norris Cotton Cancer Center ...

Molecular changes with age in normal breast tissue are linked to cancer-related changes

July 20, 2017
Several known factors are associated with a higher risk of breast cancer including increasing age, being overweight after menopause, alcohol intake, and family history. However, the underlying biologic mechanisms through ...

Immune-cell numbers predict response to combination immunotherapy in melanoma

July 20, 2017
Whether a melanoma patient will better respond to a single immunotherapy drug or two in combination depends on the abundance of certain white blood cells within their tumors, according to a new study conducted by UC San Francisco ...

Discovery could lead to better results for patients undergoing radiation

July 19, 2017
More than half of cancer patients undergo radiotherapy, in which high doses of radiation are aimed at diseased tissue to kill cancer cells. But due to a phenomenon known as radiation-induced bystander effect (RIBE), in which ...

Definitive genomic study reveals alterations driving most medulloblastoma brain tumors

July 19, 2017
The most comprehensive analysis yet of medulloblastoma has identified genomic changes responsible for more than 75 percent of the brain tumors, including two new suspected cancer genes that were found exclusively in the least ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.