Summary of Study ST002835

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 PR001775. The data can be accessed directly via it's Project DOI: http://dx.doi.org/10.21228/M88M6V This work is supported by NIH grant, U2C- DK119886.

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This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

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Study IDST002835
Study TitleInvestigation of FGFR signaling controlled metabolism in FGFR2-fusion+ intrahepatic cholangiocarcinoma
Study SummaryGenomic alterations that activate FGFR2 are common in intrahepatic cholangiocarcinoma (ICC) and confer sensitivity to treatment with FGFR inhibitors. However, the depth and duration of responses are often limited. Elucidating the FGFR2-driven oncogenic program and the adaptions to FGFR inhibition is needed to gain insight into the biology of these tumors and inform future therapeutic development. Here, we conducted metabolomic analysis of patient-derived models to define the pathways that fuel tumor growth downstream of oncogenic FGFR2 signaling in ICC and to uncover compensatory mechanisms associated with pathway inhibition. We find FGFR2-fusion+ ICC maintains a highly glycolytic phenotype in FGFR2+ ICC. Conversely, FGFR inhibition blocks glucose uptake and glycolysis, while inciting a series of adaptive changes. Thus, we show that glycolysis is a key downstream effector of oncogenic FGFR2 signaling in ICC, and that pronounced metabolic reprogramming in response to FGFR inhibition confers new targetable vulnerabilities.
Institute
Massachusetts General Hospital
Last NameZhen
First NameYuanli
Address185 cambridge street, room 4100
Emailyzhen1@mgh.harvard.edu
Phone4698792279
Submit Date2023-08-26
Raw Data AvailableYes
Raw Data File Type(s)mzML
Analysis Type DetailLC-MS
Release Date2024-03-20
Release Version1
Yuanli Zhen Yuanli Zhen
http://dx.doi.org/10.21228/M88M6V
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Combined analysis:

Analysis ID AN004631 AN004632
Analysis type MS MS
Chromatography type HILIC HILIC
Chromatography system Thermo Vanquish Thermo Vanquish
Column Thermo BETASIL Diol (150 x 2.1mm,5um) Thermo BETASIL Diol (150 x 2.1mm,5um)
MS Type ESI ESI
MS instrument type Orbitrap Orbitrap
MS instrument name Thermo Orbitrap ID-X tribrid Thermo Orbitrap ID-X tribrid
Ion Mode POSITIVE NEGATIVE
Units area analyzed by Compound discoverer (counts x seconds) area analyzed by Compound discoverer (counts x seconds)
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