Summary of Study ST002847
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001782. The data can be accessed directly via it's Project DOI: 10.21228/M8CB14 This work is supported by NIH grant, U2C- DK119886. See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Study ID | ST002847 |
| Study Title | Targeting Pancreatic Cancer Metabolic Dependencies through Glutamine Antagonism. |
| Study Summary | Pancreatic ductal adenocarcinoma (PDAC) cells utilize glutamine (Gln) to support proliferation and redox balance. Earlier 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 various in vivo models using DRP-104 (sirpiglenastat), a pro-drug version of DON that was designed to circumvent DON associated toxicity. We found that ERK signaling is increased as a compensatory mechanism. Combinatorial treatment of DRP-104 and Trametinib led to a significant increase in survival in a syngeneic model 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. |
| Institute | New York University |
| Last Name | Encarnacion Rosado |
| First Name | Joel |
| Address | Smilow Research Building Room 907G New York, NY 10016 |
| jencarnacionrosado@salk.edu, Alec.Kimmelman@nyulangone.org | |
| Phone | 646-501-8984 |
| Submit Date | 2023-09-06 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | mzXML |
| Analysis Type Detail | LC-MS |
| Release Date | 2024-09-08 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Treatment:
| Treatment ID: | TR002968 |
| Treatment Summary: | HY19636 cells were plated in a six-well plate at 2.0x10^5 cells/well and allowed to attach overnight in DMEM. Next, cells were washed with PBS twice and cultured for 24 hours in DMEM supplemented with 10% dialyzed serum was added. Cells were pre-treated with DON (25µM) or DRP-104 (25µM) overnight, media was removed and washed with PBS. Then, cells were frozen in -80C and until metabolite extraction |
