Pancreatic cancers appear to be vulnerable to a drug combination that starves tumors of a key nutrient, according to a study performed in mice.
The approach appears promising enough that researchers at Sanford Burnham Prebys Medical Discovery Institute say they’re arranging for a clinical trial in patients. They are meeting with oncologists at Oregon Health and Science University to plan the trial.
A cancer researcher not involved in the study said its findings make a clinical trial worth performing in patients with pancreatic cancer, one of the most deadly forms of the disease. More information about the trial will be released when it receives approval.
Researchers led by Ze’ev Ronai of the institute used a drug to deprive the tumors of asparagine, a protein component or amino acid. The drug, called L-asparaginase, is approved for certain forms of leukemia.
Reducing the amount of available asparagine, named for its isolation from asparagus, inhibits cancer growth. But cancers treated with the drug alone usually develop the ability to make their own asparagine.
So the researchers added a second drug that shuts off this metabolic pathway. The result was that the tumors shrank in mice treated with the combo therapy.
The study was published Monday in Nature Cell Biology. Go to j.mp/sbpcancer for the complete study.
One of the study’s key findings was identifying the precise molecular mechanism asparagine-deprived cancers use, “thus providing the molecular basis for rational combination therapies that rely on asparagine restriction strategies.”
In this instance, the researchers added a drug approved to treat melanoma, in a class of drugs called MEK inhibitors. Melanomas also shrank with the combo therapy.
David K. Ann, a City of Hope cancer scientist who studies cancer metabolism, said the study provides enough evidence to justify testing the combo therapy in patients,
“It’s probably a major discovery by this group of investigators,” said Ann who is Dean of the Irell and Manella Graduate School of Biological Sciences at the Duarte-based medical center. “I think they’re doing the right thing.”
The mouse study provided “proof of principle,” Ann said. The next step should be to go to a small number of patients to test whether the concept works in people.
The study highlights the complexity of treating cancer, Rosalie C. Sears, a professor of molecular and medical genetics at Oregon Health & Science University, said in a statement.
“It’s clear we’re not going to find a single magic bullet that cures cancer but will instead need several drugs that target multiple vulnerabilities,” Sears said. “This study identifies a promising dual treatment for pancreatic cancer — one of the deadliest cancers — and I look forward to seeing these drugs tested in patients.”
The study was funded by the National Institutes of Health and the Hevery Foundation.
This content was originally published here.
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