Metabolic Pathway May Reveal Optimal Pancreatic Cancer Drug Combination

By tracking metabolic pathways favored by cancer cells, researchers found that an anti-cancer drug combination can help treat pancreatic cancer.

In a study published in the Proceedings of the National Academy of Sciences, researchers injected the experimental drug BPTES into mice with implanted human pancreatic tumors. Although this drug has been used in animal models for other types of cancers, it has not been able to substantially reduce tumor sizes.

Researchers believed this was a result of the drug concentration in tumor tissue not being high enough with conventional drug formulation methods. Investigators used this knowledge to encapsulate BPTES in a nanoparticle capsule coated in polyethylene glycol using a method that provided a more uniform coating.

The results of the study showed that after 16 days, 8 BPTES-treated mice had tumors that were half the size of another 8 mice treated with nanoparticles that did not contain any drugs. When BPTES was not encased in the nanoparticle delivery system, researchers found that it had little effect on the tumor size in the mice.

“This shows that the nanoparticle-encapsulated drug is more effective in tumor reduction than the drug alone in these animal models,” said researcher Anne Le, MD, HDR.

Once researchers saw the tumors shrunk by half, they began searching for which major metabolic pathway was driving the growth of the remaining half of the tumor. To do this, researchers injected the 8 mice that had tumors with high levels of labeled glutamine and glucose, a metabolic compound commonly linked to pancreatic cancer growth.

Next, they traced the biochemical breakdown of the compound through the mice, which revealed that the remaining tumors cells had high amounts of lactate, according to the study. Upon this finding, researchers tested the glucose-blocking anti-diabetes drug metformin in combination with the nanoparticle-encapsulated BPTES, on an additional 8 mice with human pancreatic tumors.

The results of the drug combination caused the tumors to shrink by at least 50% more than mice treated with either of the drugs alone. Although, other studies have tested metformin in pancreatic cancer patients, little success has been achieved.

“But it appears the key may be to combine it with other drugs to shut off multiple key pathways in those tumors,” Le said.

As of now, scientists have filed a patent for the technology associated with nanoparticle-encapsulated BPTES.