Asset Details
Do you wish to reserve the book?
Targeting pancreatic cancer metabolic dependencies through glutamine antagonism
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Targeting pancreatic cancer metabolic dependencies through glutamine antagonism
Do you wish to request the book?
Targeting pancreatic cancer metabolic dependencies through glutamine antagonism
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Targeting pancreatic cancer metabolic dependencies through glutamine antagonism
2024
Overview
Pancreatic ductal adenocarcinoma (PDAC) cells use glutamine (Gln) to support proliferation and redox balance. Early attempts to inhibit Gln metabolism using glutaminase inhibitors resulted in rapid metabolic reprogramming and therapeutic resistance. Here, we demonstrated that treating PDAC cells with a Gln antagonist, 6-diazo-5-oxo- l -norleucine (DON), led to a metabolic crisis in vitro. In addition, we observed a profound decrease in tumor growth in several in vivo models using sirpiglenastat (DRP-104), a pro-drug version of DON that was designed to circumvent DON-associated toxicity. We found that extracellular signal-regulated kinase (ERK) signaling is increased as a compensatory mechanism. Combinatorial treatment with DRP-104 and trametinib led to a significant increase in survival in a syngeneic model of PDAC. These proof-of-concept studies suggested that broadly targeting Gln metabolism could provide a therapeutic avenue for PDAC. The combination with an ERK signaling pathway inhibitor could further improve the therapeutic outcome.
Publisher
Nature Publishing Group,Nature Publishing Group US
Subject
Antineoplastic Agents - pharmacology
/ Carbon
/ Carcinoma, Pancreatic Ductal - drug therapy
/ Carcinoma, Pancreatic Ductal - metabolism
/ Enzyme Inhibitors - pharmacology
/ Glucose
/ Humans
/ Hypoxia
/ Kinases
/ Lipids
/ Nitrogen
/ Pancreatic Neoplasms - drug therapy
/ Pancreatic Neoplasms - metabolism
/ Tumors
