Sanford Burnham Prebys Breakthrough as Asparagine & MEK Inhibitor Comb Therapy Zaps Pancreatic Cancer Tumors

Nov 19, 2019 | Asparagine, MEK Inhibitors, Pancreatic Cancer

Sanford Burnham Prebys Breakthrough as Asparagine & MEK Inhibitor Comb Therapy Zaps Pancreatic Cancer Tumors

Preclinical investigators at Sanford Burnham Prebys Medical Discovery Institute as well as others including the NIH report that pancreatic cancers are vulnerable to a drug combination that actually starves the cancerous tumors of a key nutrient as concluded from research preclinical research. The combination includes asparagine and use of a MEK inhibitor.

Planning a Clinical Trial

In fact the results are so promising that the Sanford Burnham Prebys Medical Discovery Institute will plan a clinical trial for studying this drug combination in humans. They are presently meeting with Oregon Health and Science University oncologists to plan the clinical trial.

A Dangerous Situation when Present

This is a deadly disease—actually one of the deadliest forms of cancer.  According to Cancer.NET, an estimated 56,770 adults in America will be diagnosed with pancreatic cancer. Although the disease represents only 3% of all cancers it is a particularly dangerous one. African Americans are at greater risk: incident rates are 25% higher in this population than among white people.  In total 45,750 will die from pancreatic cancer this year in the United States. It accounts for 7% of all cancer deaths. Most pancreatic cancers are called exocrine adenocarcinoma.  The 5-year survivor rate for pancreatic cancer is 9%.

Preclinical Research: Combination Therapy Shrinks Tumors in Mice

The research team utilized 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.  Named as it was isolated from asparagus, the reduction of available asparagine inhibits cancer growth. However cancers have a way to fight back—namely they can produce their own asparagine hence counteracting the drug.

Hence researchers at Sanford Burnham Prebys Medical Discovery Institute included a second drug to effectively shut off this metabolic pathway. The team found that the results were promising in mice: the tumors shrank when treated with this combination therapy. Thereafter, the team published the results in Nature Cell Biology.

In the study the team was able to identify the more precise molecular mechanism asparagine-deprived cancers use to produce asparagine and survive. Hence, in this instance the research team included a drug approved to treat melanoma from a class of drugs called MEK inhibitors.  The combo therapy also shrank melanoma tumors in mice.

A “Synergistic Attack”

Eytan Ruppin, MD, PhD, a study author and chief of the Cancer Data Science Library at the National Cancer Institute reports, “This research lays the basis for inhibition of pancreatic tumor growth by a combined synergistic attack based on asparagine restriction and MAPK signaling inhibition.”

Study Funding

The study was funded by the National Institutes of Health and the Hervey Foundation

Lead Research/Investigator

Ze’ev Ronai, PhD, Chief Scientific Advisor, Sanford Burnham Prebys Medical Discovery Institute

Call to Action: TrialSite News will be following this imminent clinical research including the principal investigator Ze’ev Ronai, PhD. See below for contact.


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