ArticleCell chemical biology2023
Screening in serum-derived medium reveals differential response to compounds targeting metabolism.
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Article in Cell chemical biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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21citing papers in PubMed
6.2field-weighted citation impact, top 3% of its field
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Who cites it
21 citing papers in PubMed, 28 citations in OpenAlex.
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- Metabolite profiling of human renal cell carcinoma reveals tissue-origin dominance in nutrient availability.eLife · 2024Article
- De Novo Purine Metabolism is a Metabolic Vulnerability of Cancers with Low p16 Expression.Cancer research communications · 2024Article
- Metabolite profiling of human renal cell carcinoma reveals tissue-origin dominance in nutrient availability.bioRxiv : the preprint server for biology · 2024Article
- Metabolic instruction of the graft-versus-leukemia immunity.Frontiers in immunology · 2024Review
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Authors and funding
34 authors at 13 institutions in 5 countries.
Keene L AbbottKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Ahmed AliKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Dominick CasalenaNovartis Institute for BioMedical Research, Cambridge, MA 02139, USA.
Brian T DoKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Harvard-MIT Health Sciences and Technology, Cambridge, MA 02139, USA.
Raphael FerreiraDepartment of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Jaime H CheahKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Christian K SouleKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Amy DeikBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Tenzin KunchokWhitehead Institute for Biomedical Research, Cambridge, MA 02139, USA.
Daniel R SchmidtKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
Steffen RennerNovartis Institutes for BioMedical Research, 4056 Basel, Switzerland.
Sophie E HonederKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Diagnostic and Research Institute of Pathology, Medical University of Graz, Graz, Austria.
Michelle WuKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Sze Ham ChanWhitehead Institute for Biomedical Research, Cambridge, MA 02139, USA.
Tenzin TseyangWhitehead Institute for Biomedical Research, Cambridge, MA 02139, USA.
Andrew T StoltzfusDepartment of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, MD 21201, USA.
Sarah L J MichelDepartment of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, MD 21201, USA.
Daniel GreavesCambridge Institute of Therapeutic Immunology & Infectious Disease, University of Cambridge, Cambridge CB2 0AW, UK; Department of Medicine, University of Cambridge, Cambridge CB2 0QQ, UK.
Peggy P HsuKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Dana-Farber Cancer Institute, Boston, MA 02115, USA; Massachusetts General Hospital Cancer Center, Boston, MA 02113, USA.
Christopher W NgKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Chelsea J ZhangKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Ali FarsidjaniNovartis Institute for BioMedical Research, Cambridge, MA 02139, USA.
Johnathan R KentDepartment of Surgery, University of Chicago Medicine, Chicago, IL 60637, USA.
Maria Lucia L MadariagaDepartment of Surgery, University of Chicago Medicine, Chicago, IL 60637, USA.
Iva Monique T GramatikovKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
Nicholas J MathesonKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Cambridge Institute of Therapeutic Immunology & Infectious Disease, University of Cambridge, Cambridge CB2 0AW, UK; Department of Medicine, University of Cambridge, Cambridge CB2 0QQ, UK.
Caroline A LewisWhitehead Institute for Biomedical Research, Cambridge, MA 02139, USA.
Clary B ClishBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Matthew G ReesBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Jennifer A RothBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Lesley Mathews GrinerNovartis Institute for BioMedical Research, Cambridge, MA 02139, USA.
Alexander MuirBen May Department of Cancer Research, University of Chicago, Chicago, IL 60637, USA.
Douglas S AuldNovartis Institute for BioMedical Research, Cambridge, MA 02139, USA.
Matthew G Vander HeidenKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Dana-Farber Cancer Institute, Boston, MA 02115, USA. Electronic address: mvh@mit.edu.
Broad Institute · USNovartis (United States) · USWhitehead Institute for Biomedical Research · USMassachusetts Institute of Technology · USUniversity of Chicago · USBeth Israel Deaconess Medical Center · USUniversity of Cambridge · GBUniversity of Maryland, Baltimore · USHarvard–MIT Division of Health Sciences and Technology · USHarvard University · USMassachusetts General Hospital · USMedical University of Graz · ATNovartis (Switzerland) · CH
Funding
VIRUS PRODUCTION COREP30CA014051 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI Kristin A Knouse · 1985 to 2026
$93.9MMedical Scientist Training ProgramT32GM007753 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI WALENSKY, LOREN DAVID · 1985 to 2021
$50.0MPRE-DOCTORAL TRAINING IN THE BIOLOGICAL SCIENCEST32GM007287 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI BELL, STEPHEN P., KEATING, AMY E · 1985 to 2019
$40.8MTumor and Circulating Markers as Links Between Obesity and Lethal Prostate CanceP50CA090381 · NCI · DANA-FARBER CANCER INSTITUTE · PI KANTOFF, PHILIP W · 2002 to 2017
$36.2MROLE OF DIETARY CONSTITUENTS ON GENE EXPRESSION IN INTESTINAL EPITHELIUMP30DK040561 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI Elizabeth Austen Lawson, Takara Leah Stanley · 1994 to 2026
$31.6MMedical Scientist Training ProgramT32GM144273 · NIGMS · HARVARD MEDICAL SCHOOL · PI David Shumway Jones, Jacqueline A. Lees · 2022 to 2026
$14.7MTraining Program in Cancer Biology and TherapeuticsT32CA071345 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI Daniel A. Haber, Lecia V. Sequist · 1997 to 2026
$10.6MInstitutional Career Development CoreKL2TR002542 · NCATS · HARVARD MEDICAL SCHOOL · PI BREDELLA, MIRIAM ANTOINETTE, RUTKOVE, SEWARD B. · 2018 to 2022
$8.7MUnderstanding the role of metabolism in cancerR35CA242379 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI VANDER HEIDEN, MATTHEW G. · 2019 to 2025
$5.8MTargeting physical stress-driven mechanisms to overcome glioblastoma treatment resistanceU01CA261842 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI JAIN, RAKESH K., MUNN, LANCE L. · 2021 to 2025
$3.1MReprogramming PDAC tumor microenvironment to improve immunotherapyU01CA224348 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI BOUCHER, YVES, JAIN, RAKESH K. · 2017 to 2021
$2.9MImproving treatment of HER2+ breast cancer brain metastasis by targeting lipid metabolismR01CA259253 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI JAIN, RAKESH K., VANDER HEIDEN, MATTHEW G. · 2021 to 2025
$2.3MDepartment of HealthHoward Hughes Medical InstituteMedical Research Council MR/T032413/1NCATS NIH HHS KL2 TR002542NCI NIH HHS F31 CA271787NCI NIH HHS P30 CA014051NCI NIH HHS P50 CA090381NCI NIH HHS R01 CA259253NCI NIH HHS R01 CA269672NCI NIH HHS R35 CA242379NCI NIH HHS T32 CA071345NCI NIH HHS U01 CA224348NCI NIH HHS U01 CA261842NHLBI NIH HHS F30 HL156404NIDDK NIH HHS P30 DK040561NIGMS NIH HHS T32 GM007287NIGMS NIH HHS T32 GM007753NIGMS NIH HHS T32 GM144273Wellcome TrustWellcome Trust 110302/Z/15/ZWellcome Trust 204845/Z/16/Z
Abstract
A challenge for screening new anticancer drugs is that efficacy in cell culture models is not always predictive of efficacy in patients. One limitation of standard cell culture is a reliance on non-physiological nutrient levels, which can influence cell metabolism and drug sensitivity. A general assessment of how physiological nutrients affect cancer cell response to small molecule therapies is lacking. To address this, we developed a serum-derived culture medium that supports the proliferation of diverse cancer cell lines and is amenable to high-throughput screening. We screened several small molecule libraries and found that compounds targeting metabolic enzymes were differentially effective in standard compared to serum-derived medium. We exploited the differences in nutrient levels between each medium to understand why medium conditions affected the response of cells to some compounds, illustrating how this approach can be used to screen potential therapeutics and understand how their efficacy is modified by available nutrients.
Indexed as
Cell Culture TechniquesHigh-Throughput Screening AssaysCell LineHumansSmall Molecule LibrariesSmall Molecule LibrariesCancer cell metabolismCulture mediaDrug sensitivityHigh-throughput screeningNutrient environmentPhenotypic drug screeningPhysiologic media
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