July 21, 2024
Pancreatic Cancer

Novel Combination of Drugs Shows Promise in Reducing Pancreatic Cancer Growth in Mice

Researchers from NYU Grossman School of Medicine have discovered a new combination of treatments that safely decreases the growth of pancreatic cancer in mice. The study, published in Nature Cancer, focuses on targeting the alternate fuel sources that pancreatic cancer cells use to sustain rapid tumor growth.

Pancreatic cancer cells have the ability to switch fuels when resources such as oxygen, blood sugar, and other nutrients become scarce due to the dense tumors cutting off their blood supply. The researchers aimed to prevent pancreatic ductal adenocarcinoma (PDAC) cells from switching to one such alternative fuel source known as glutamine.

PDAC cells use an enzyme called glutaminase to convert the amino acid glutamate into glutamine, which can be burned for fuel. The researchers tested a drug called DRP-104, which was designed to inhibit the action of glutamine. While previous attempts to block glutaminase have caused cancer cells to switch to other scavenging pathways, DRP-104 showed promising results in decreasing the growth of PDAC cells in mouse models.

In addition to inhibiting glutamine metabolism in cancer cells, the researchers found that DRP-104 led to an increase in signaling through a protein called extracellular signal-regulated kinase or ERK. To further enhance the effects of DRP-104, the researchers combined it with trametinib, an existing drug that blocks the ERK signaling pathway. This combination improved survival rates in mouse models of pancreatic cancer compared to treatment with DRP-104 alone.

Moving forward, the research team plans to investigate how targeting glutamine antagonism affects other nutrient scavenging mechanisms in pancreatic cancer cells. The success of these approaches will require careful balancing of therapeutic efficacy and potential toxicity effects on normal tissues.

The study was funded by the Perlmutter Cancer Center support grant P30CA016087, National Cancer Institute grants, the Lustgarten Foundation, Stand Up to Cancer, and the Howard Hughes Medical Gilliam Fellowships.

Lead researcher, Dr. Alec Kimmelman, has disclosed financial interests in Vescor Therapeutics, Rafael/Cornerstone Pharmaceuticals, OncoRev, Deciphera, and Abbvie, and these relationships are managed according to the policies of NYU Langone Health. The study’s authors include Joel Encarnaci├│n-Rosado, Albert Sohn, Douglas Biancur, Elaine Lin, Victoria Osorio-Vasquez, Diana Gonz├ílez-Baerga, Ende Zhao, Diane Simeone, Tori Rodrick, Drew Jones, Seth Parker, Yumi Yokoyama, and Robert Wild, from various institutions including NYU Grossman School of Medicine, University of British Columbia, and Dracen Pharmaceuticals. Yokoyama and Wild are employees and have ownership in Dracen Pharmaceuticals, which developed DRP-104.

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