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.

See: https://www.metabolomicsworkbench.org/about/howtocite.php

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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Factors:

Subject type: Cultured cells; Subject species: Homo sapiens (Factor headings shown in green)

mb_sample_id local_sample_id cell line treatment labeling status
SA307239SUB11589p2_Spl09ICC13-7 control 13C6-Glucose Isotopic tracing 0h as ctrl
SA307240SUB11589p2_Spl07ICC13-7 control 13C6-Glucose Isotopic tracing 0h as ctrl
SA307241SUB11589p2_Spl08ICC13-7 control 13C6-Glucose Isotopic tracing 0h as ctrl
SA307242SUB11589p2_Spl15ICC13-7 control 13C6-Glucose Isotopic tracing 1h
SA307243SUB11589p2_Spl14ICC13-7 control 13C6-Glucose Isotopic tracing 1h
SA307244SUB11589p2_Spl16ICC13-7 control 13C6-Glucose Isotopic tracing 1h
SA307245SUB11589p2_Spl20ICC13-7 control 13C6-Glucose Isotopic tracing 24h
SA307246SUB11589p2_Spl21ICC13-7 control 13C6-Glucose Isotopic tracing 24h
SA307247SUB11589p2_Spl22ICC13-7 control 13C6-Glucose Isotopic tracing 24h
SA307230SUB11589p2_Spl12ICC13-7 Infigratinib 13C6-Glucose Isotopic tracing 0h as ctrl
SA307231SUB11589p2_Spl10ICC13-7 Infigratinib 13C6-Glucose Isotopic tracing 0h as ctrl
SA307232SUB11589p2_Spl11ICC13-7 Infigratinib 13C6-Glucose Isotopic tracing 0h as ctrl
SA307233SUB11589p2_Spl17ICC13-7 Infigratinib 13C6-Glucose Isotopic tracing 1h
SA307234SUB11589p2_Spl18ICC13-7 Infigratinib 13C6-Glucose Isotopic tracing 1h
SA307235SUB11589p2_Spl19ICC13-7 Infigratinib 13C6-Glucose Isotopic tracing 1h
SA307236SUB11589p2_Spl24ICC13-7 Infigratinib 13C6-Glucose Isotopic tracing 24h
SA307237SUB11589p2_Spl25ICC13-7 Infigratinib 13C6-Glucose Isotopic tracing 24h
SA307238SUB11589p2_Spl23ICC13-7 Infigratinib 13C6-Glucose Isotopic tracing 24h
SA307248SUB11589p2_Spl32ICC21 Afatinib N/A
SA307249SUB11589p2_Spl33ICC21 Afatinib N/A
SA307250SUB11589p2_Spl34ICC21 Afatinib N/A
SA307251SUB11589p2_Spl36ICC21 Combo N/A
SA307252SUB11589p2_Spl37ICC21 Combo N/A
SA307253SUB11589p2_Spl35ICC21 Combo N/A
SA307257SUB11589p2_Spl28ICC21 control N/A
SA307258SUB11589p2_Spl26ICC21 control N/A
SA307259SUB11589p2_Spl27ICC21 control N/A
SA307254SUB11589p2_Spl29ICC21 Infigratinib N/A
SA307255SUB11589p2_Spl30ICC21 Infigratinib N/A
SA307256SUB11589p2_Spl31ICC21 Infigratinib N/A
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