Evidence map›Paper›PMID 28564604›Full record

ArticleCell reports2017

Cancer-Associated IDH1 Promotes Growth and Resistance to Targeted Therapies in the Absence of Mutation.

Andrea E Calvert, Alexandra Chalastanis, Yongfei Wu, Lisa A Hurley, Fotini M Kouri, Yingtao Bi, Maureen Kachman, Jasmine L May, Elizabeth Bartom, Youjia Hua and 12 more

Open access · goldAbstract read
In one paragraph

Article in Cell reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 127 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
127citing papers in PubMed, 1 pooled it
11.5field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

127 citing papers in PubMed, 1 synthesis or guideline pooled it, 204 citations in OpenAlex.

  1. Pooled it
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  4. Article
  5. Astrocytic GPR55 receptors promote glycolysis.Journal of cannabis research · 2026
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67 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

22 authors at 5 institutions in 1 country.

Andrea E CalvertKen and Ruth Davee Department of Neurology, The Northwestern Brain Tumor Institute, The Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, International Institute for Nanotechnology, Northwestern University, Chicago, IL 60611, USA.
Alexandra ChalastanisKen and Ruth Davee Department of Neurology, The Northwestern Brain Tumor Institute, The Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, International Institute for Nanotechnology, Northwestern University, Chicago, IL 60611, USA.
Yongfei WuKen and Ruth Davee Department of Neurology, The Northwestern Brain Tumor Institute, The Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, International Institute for Nanotechnology, Northwestern University, Chicago, IL 60611, USA.
Lisa A HurleyKen and Ruth Davee Department of Neurology, The Northwestern Brain Tumor Institute, The Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, International Institute for Nanotechnology, Northwestern University, Chicago, IL 60611, USA.
Fotini M KouriKen and Ruth Davee Department of Neurology, The Northwestern Brain Tumor Institute, The Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, International Institute for Nanotechnology, Northwestern University, Chicago, IL 60611, USA.
Yingtao BiDivision of Health and Biomedical Informatics, Department of Preventive Medicine, The Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Maureen KachmanMichigan Regional Comprehensive Metabolomics Resource Core, University of Michigan, Ann Arbor, MI 48105, USA.
Jasmine L MayKen and Ruth Davee Department of Neurology, The Northwestern Brain Tumor Institute, The Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, International Institute for Nanotechnology, Northwestern University, Chicago, IL 60611, USA.
Elizabeth BartomDepartment of Biochemistry and Molecular Genetics, Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Youjia HuaDivision of Hematology/Oncology, The Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Rama K MishraCenter for Molecular Innovation and Drug Discovery, Northwestern University, Evanston, IL 60208, USA.
Gary E SchiltzCenter for Molecular Innovation and Drug Discovery, Northwestern University, Evanston, IL 60208, USA; Department of Pharmacology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL 60611, USA.
Oleksii DubrovskyiChemistry of Life Processes Institute, Northwestern University, Evanston, IL 60208, USA.
Andrew P MazarChemistry of Life Processes Institute, Northwestern University, Evanston, IL 60208, USA.
Marcus E PeterDivision of Hematology/Oncology, The Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Hongwu ZhengCold Spring Harbor Laboratories, Cold Spring Harbor, NY 11724, USA.
C David JamesDepartment of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Charles F BurantMichigan Regional Comprehensive Metabolomics Resource Core, University of Michigan, Ann Arbor, MI 48105, USA.
Navdeep S ChandelDepartment of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60615, USA.
Ramana V DavuluriDivision of Health and Biomedical Informatics, Department of Preventive Medicine, The Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Craig HorbinskiDepartment of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA; Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60615, USA.
Alexander H SteghKen and Ruth Davee Department of Neurology, The Northwestern Brain Tumor Institute, The Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, International Institute for Nanotechnology, Northwestern University, Chicago, IL 60611, USA. Electronic address: a-stegh@northwestern.edu.
Northwestern University · USUniversity of Michigan–Ann Arbor · USCold Spring Harbor Laboratory · USNeurological Surgery · USRobert H. Lurie Comprehensive Cancer Center of Northwestern University

Funding

Tumor Environment and Metastasis (TEAM) Research ProgramP30CA060553 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI Daniela E Matei · 1993 to 2026
$153.9M
Single-Cell Biology Shared ResourceP30CA045508 · NCI · COLD SPRING HARBOR LABORATORY · PI John Edward Moses · 1987 to 2026
$118.9M
Project 3: Spherical Nucleic Acids as Immunotherapeutic Agents for Prostate CancerU54CA199091 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI MIRKIN, CHAD A. · 2015 to 2019
$11.7M
Statistics and Bioinformatics Core - WangU24DK097153 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI BURANT, CHARLES F · 2012 to 2017
$10.1M
CARCINOGENESIS TRAINING PROGRAMT32CA009560 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI Kathleen Janee Green · 1986 to 2026
$8.4M
Informatics Platform for Mammalian Gene Regulation at Isoform-levelR01LM011297 · NLM · WISTAR INSTITUTE · PI DAVULURI, RAMANA V · 2013 to 2020
$2.4M
NCI NIH HHS P30 CA045508NCI NIH HHS P30 CA060553NCI NIH HHS T32 CA009560NCI NIH HHS U54 CA199091NIDDK NIH HHS U24 DK097153NLM NIH HHS R01 LM011297
6 · The paper itself

Abstract

Oncogenic mutations in two isocitrate dehydrogenase (IDH)-encoding genes (IDH1 and IDH2) have been identified in acute myelogenous leukemia, low-grade glioma, and secondary glioblastoma (GBM). Our in silico and wet-bench analyses indicate that non-mutated IDH1 mRNA and protein are commonly overexpressed in primary GBMs. We show that genetic and pharmacologic inactivation of IDH1 decreases GBM cell growth, promotes a more differentiated tumor cell state, increases apoptosis in response to targeted therapies, and prolongs the survival of animal subjects bearing patient-derived xenografts (PDXs). On a molecular level, diminished IDH1 activity results in reduced α-ketoglutarate (αKG) and NADPH production, paralleled by deficient carbon flux from glucose or acetate into lipids, exhaustion of reduced glutathione, increased levels of reactive oxygen species (ROS), and enhanced histone methylation and differentiation marker expression. These findings suggest that IDH1 upregulation represents a common metabolic adaptation by GBMs to support macromolecular synthesis, aggressive growth, and therapy resistance.

Indexed as

Drug Resistance, NeoplasmMolecular Targeted TherapyAnimalsApoptosisCell DifferentiationCell ProliferationDisease ProgressionErlotinib HydrochlorideForkhead Transcription FactorsGene Expression Regulation, NeoplasticGene Knockdown TechniquesGlioblastomaHistonesIsocitrate DehydrogenaseKetoglutaric AcidsLipidsErlotinib HydrochlorideForkhead Transcription FactorsFOXO6 protein, humanHistonesIsocitrate DehydrogenaseKetoglutaric AcidsLipidsNADPProtein Kinase InhibitorsReactive Oxygen SpeciesRNA, MessengerdifferentiationEGFRGBMlipidsmetabolismNADPHreactive oxygen species (ROS)targeted therapywild-type IDH1

Identifiers

PMID28564604
PMCPMC5564207
OpenAlexW2620446315

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.