Researchers at NYU Grossman School of Medicine and the Perlmutter Cancer Center have discovered a promising combination of treatments that effectively reduced the growth of pancreatic cancer in mice.
By preventing cancer cells from scavenging for fuel, this approach aims to curtail the rapid growth of pancreatic tumors.
The Challenge of Pancreatic Cancer
Pancreatic cancer poses a significant challenge due to its aggressive nature. As tumors grow, they outstrip their own blood supply, leading to a scarcity of essential resources such as oxygen and blood sugar.
In response, cancer cells adapt by switching to alternative fuel sources, a process that contributes to the lethality of pancreatic cancers.
Targeting a Critical Switch
The study, published in Nature Cancer, focuses on blocking a specific switch that pancreatic cancer cells use to sustain their growth.
These cells employ an enzyme called glutaminase to convert the amino acid glutamate into glutamine, a form of fuel that supports rapid tumor growth.
Traditional drugs designed to block glutaminase have limitations as they can cause cancer cells to switch to other scavenging pathways.
An Innovative Approach: DRP-104
To overcome these challenges, the researchers explored an experimental treatment called DRP-104, developed by Dracen Pharmaceuticals.
DRP-104 is a “prodrug” form of the compound 6-Diazo-5-oxo-L-norleucine (DON). This drug is designed to be preferentially activated within tumors, mitigating toxicity concerns associated with DON.
Unlike traditional glutaminase blockers, DON mimics glutamine and broadly inhibits all metabolic pathways that use glutamine, effectively starving cancer cells.
Improved Survival through Combination
The study found that DRP-104 treatment alone reduced the growth of pancreatic ductal adenocarcinoma (PDAC) in mouse models.
Moreover, when combined with trametinib, an existing drug that blocks the ERK signaling pathway, it significantly improved survival compared to DRP-104 treatment alone.
PDAC cells exposed to DRP-104 increased signaling through the extracellular signal-regulated kinase (ERK) pathway to compensate for the loss of glutamine metabolism.
A New Hope for Pancreatic Cancer Treatment
Dr. Alec Kimmelman, the study’s corresponding author, emphasized the significance of these findings.
Despite advances in understanding how cancer cells switch fuel sources, translating this knowledge into effective therapies has been challenging.
The approach of broadly antagonizing metabolic pathways with glutamine analogs offers promise and is already being tested in clinical trials.
The research team will continue investigating how antagonizing glutamine impacts other adaptive nutrient scavenging mechanisms in pancreatic cancer.
Striking the right balance between therapeutic efficacy and potential side effects on normal tissues will be crucial as they advance this promising approach in clinical trials.
In summary, this study offers hope for improved treatments for pancreatic cancer by targeting the cancer cells’ ability to switch fuel sources, potentially leading to better outcomes for patients in the future.
If you care about cancer, please read studies that a low-carb diet could increase overall cancer risk, and vitamin D supplements could strongly reduce cancer death.
For more information about health, please see recent studies about how drinking milk affects the risks of heart disease and cancer and results showing higher intake of dairy foods linked to higher prostate cancer risk.
The research findings can be found in Nature Cancer.
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