ArticleCancer discovery2020
Limited Environmental Serine and Glycine Confer Brain Metastasis Sensitivity to PHGDH Inhibition.
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Article in Cancer discovery, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 182 papers, 1 of them a synthesis that pooled it.
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182citing papers in PubMed, 1 pooled it
12.5field-weighted citation impact, top 1% of its field
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Who cites it
182 citing papers in PubMed, 1 synthesis or guideline pooled it, 280 citations in OpenAlex.
- Brain metastases: A Society for Neuro-Oncology (SNO) consensus review on current management and future directions.Neuro-oncology · 2022Guideline
- Local production of lactate, ribose phosphate, and amino acids within human triple-negative breast cancer.Med (New York, N.Y.) · 2021Trial
- Metabolites and cancer metastasis.Oncogene · 2026Review
- Serine Starvation Modulates mRNA Splicing through Translational Inhibition of SRSF Proteins.Cancer research · 2026Article
- Metabolic immune checkpoints (MICs) in cancer: from molecular mechanisms to challenges and opportunities in clinical translation.Signal transduction and targeted therapy · 2026Review
- Macrophage-supported metabolic adaptation drives tumor survival under nutrient stress.Science advances · 2026Article
- Inhibition of the lipocalin-2-phosphatidylserine axis restores natural killer cell immune surveillance.Cell reports. Medicine · 2026Article
- PHGDH in cancer: a narrative review of its functions beyond serine metabolism.Translational cancer research · 2026Review
- Copper depletion boosts CNS leukemia therapy by inhibiting nucleotide synthesis through impairment of mitochondrial complex IV activity.Nature cancer · 2026Article
- Beyond Glycolysis: Targeting Non-Glycolytic Metabolic Pathways in Brain Tumors for Therapeutic Innovation: A Narrative Review.Health science reports · 2026Article
- Dynamic remodeling of amino acid metabolism in tumor-associated macrophages: Fueling immunosuppression, reshaping tumor niches, and unlocking metabolic checkpoints.Journal of advanced research · 2026Review
- Complex I protein NDUFB9 is a metabolic vulnerability in triple negative breast cancer brain metastases.Nature communications · 2026Article
- Targeting the noncanonical function of metabolic enzyme PHGDH in driving PD-L1 expression and cancer immune evasion.Cell reports. Medicine · 2026Article
- Targeting MET in non-small cell lung cancer brain metastases: from molecular mechanism to precision therapy.Journal of translational medicine · 2026Review
- PHGDH is a targetable driver of PDAC progression.bioRxiv : the preprint server for biology · 2026Article
- Nanomedicine-enabled disruption of glucose metabolism and synergistic antitumor therapy.Journal of nanobiotechnology · 2026Review
- Targeting one-carbon metabolic vulnerabilities of metastasis with therapeutic potential.bioRxiv : the preprint server for biology · 2026Article
- The evolving landscape of brain metastasis: volume II.Trends in cancer · 2026Review
- Digital twins for in vivo metabolic flux estimations in patients with brain cancer.Cell metabolism · 2026Article
- PHGDH at the crossroads: metabolic plasticity, metastatic paradoxes, and therapeutic reconnaissance in cancer.Journal of biomedical science · 2026Review
122 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
40 authors at 12 institutions in 3 countries.
Bryan Ngo *Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, New York.
Eugenie Kim *Department of Radiation Oncology, Perlmutter Cancer Center and NYU Langone Health, New York, New York.
Victoria Osorio-Vasquez *Department of Radiation Oncology, Perlmutter Cancer Center and NYU Langone Health, New York, New York.ORCID 0000-0001-7956-1633
Sophia DollDepartment of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany.
Sophia BustraanDepartment of Radiation Oncology, Perlmutter Cancer Center and NYU Langone Health, New York, New York.
Roger J LiangSandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, New York.
Alba LuengoKoch Institute for Integrative Cancer Research, Cambridge, Massachusetts.
Shawn M DavidsonLewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey.
Ahmed AliKoch Institute for Integrative Cancer Research, Cambridge, Massachusetts.
Gino B FerraroEdwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts.
Grant M FischerDepartments of Translational Molecular Pathology, Melanoma Medical Oncology, Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Roozbeh EskandariDepartment of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York.
Diane S KangDepartment of Stem Cell Biology and Regenerative Medicine, University of Southern California Norris Comprehensive Cancer Center, Keck School of Medicine, Los Angeles, California.
Jing NiDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Ariana PlasgerSandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, New York.ORCID 0000-0003-4964-1389
Vinagolu K RajasekharDepartment of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York.
Edward R KastenhuberSandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, New York.
Sarah BachaSandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, New York.
Roshan K SriramSandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, New York.
Benjamin D SteinSandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, New York.
Samuel F BakhoumHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York.
Matija SnuderlDepartment of Pathology, New York University Langone Health, New York, New York.
Paolo CotziaDepartment of Pathology, New York University Langone Health, New York, New York.
John H HealeyDepartment of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York.ORCID 0000-0002-0802-1186
Nello MainolfiRaze Therapeutics, Cambridge, Massachusetts.
Vipin SuriRaze Therapeutics, Cambridge, Massachusetts.
Adam FriedmanRaze Therapeutics, Cambridge, Massachusetts.
Mark ManfrediRaze Therapeutics, Cambridge, Massachusetts.
David M SabatiniWhitehead Institute for Biomedical Research, Cambridge, Massachusetts.ORCID 0000-0002-1446-7256
Drew R JonesDepartment of Radiation Oncology, Perlmutter Cancer Center and NYU Langone Health, New York, New York.ORCID 0000-0001-8732-9818
Min YuMolecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, New York.
Jean J ZhaoDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Rakesh K JainEdwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts.ORCID 0000-0001-7571-3548
Kayvan R KeshariDepartment of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York.
Michael A DaviesDepartments of Translational Molecular Pathology, Melanoma Medical Oncology, Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas.ORCID 0000-0002-0977-0912
Matthew G Vander HeidenKoch Institute for Integrative Cancer Research, Cambridge, Massachusetts.ORCID 0000-0002-6702-4192
Eva HernandoDepartment of Pathology, New York University Langone Health, New York, New York.
Matthias MannDepartment of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany.
Lewis C CantleySandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, New York. michael.pacold@nyulangone.org lcantley@med.cornell.edu.ORCID 0000-0002-1298-7653
Michael E PacoldDepartment of Radiation Oncology, Perlmutter Cancer Center and NYU Langone Health, New York, New York. michael.pacold@nyulangone.org lcantley@med.cornell.edu.
Cornell University · USNYU Langone Health · USMemorial Sloan Kettering Cancer Center · USRaNA Therapeutics (United States) · USBroad Institute · USHarvard University · USCenter for Cancer Research · USThe University of Texas MD Anderson Cancer Center · USMax Planck Institute of Biochemistry · DEPrinceton University · USUniversity of Copenhagen · DKUniversity of Southern California · US
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4MVaccine FacilityP30CA016087 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI ANIRBAN MAITRA · 1985 to 2026
$83.1MPRE-DOCTORAL TRAINING IN THE BIOLOGICAL SCIENCEST32GM007287 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI BELL, STEPHEN P., KEATING, AMY E · 1985 to 2019
$40.8MVascular Normalization: Rolse of Perivascular CellsP01CA080124 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI JAIN, RAKESH K. · 2000 to 2016
$35.0MTargeting the Vasular SystemP50CA165962 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI WENDY Beth LONDON · 2013 to 2026
$33.5MTissue and Pathology CoreP50CA168504 · NCI · DANA-FARBER CANCER INST · PI Nabihah Tayob · 2013 to 2026
$30.1MCenter for Clinical and Translational Sciences (CCTS)UL1TR000371 · NCATS · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI MCPHERSON, DAVID D · 2012 to 2016
$13.4MProject 4P50CA225450 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI KIRCHHOFF, TOMAS · 2019 to 2025
$12.5MIntegrating targeted therapy and immunotherapy to break through cancerR35CA210057 · NCI · DANA-FARBER CANCER INST · PI Jean Zhao · 2016 to 2026
$10.8MRole of Phosphoinositides and Protein Kinases in the control of Cancer MetabolismR35CA197588 · NCI · WEILL MEDICAL COLL OF CORNELL UNIV · PI LEWIS C. CANTLEY · 2016 to 2026
$10.2MProject 3: Physical and Metabolic Constraints of Cancer Cell InvasionU54CA210184 · NCI · CORNELL UNIVERSITY · PI CANTLEY, LEWIS C., FISCHBACH, CLAUDIA · 2016 to 2020
$10.2MSex Differences in Methylome Alterations and Mutational Burden in Early Stage MelanomaP01CA206980 · NCI · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · PI BERWICK, MARIANNE, THOMAS, NANCY E. · 2017 to 2022
$10.1MHoward Hughes Medical InstituteNCATS NIH HHS TL1 TR000369NCATS NIH HHS UL1 TR000371NCI NIH HHS DP2 CA206653NCI NIH HHS F31 CA250364NCI NIH HHS F99 CA234950NCI NIH HHS K00 CA234950NCI NIH HHS K22 CA175228NCI NIH HHS K22 CA212059NCI NIH HHS P01 CA080124NCI NIH HHS P01 CA206980NCI NIH HHS P30 CA008748NCI NIH HHS P30 CA016087NCI NIH HHS P50 CA165962NCI NIH HHS P50 CA168504NCI NIH HHS P50 CA225450NCI NIH HHS R01 CA085140NCI NIH HHS R01 CA098706NCI NIH HHS R01 CA103866NCI NIH HHS R01 CA115767NCI NIH HHS R01 CA121118NCI NIH HHS R01 CA126642NCI NIH HHS R01 CA129105NCI NIH HHS R01 CA168653NCI NIH HHS R01 CA202027NCI NIH HHS R01 CA208205NCI NIH HHS R01 CA237466NCI NIH HHS R01 CA252037NCI NIH HHS R21 CA198028NCI NIH HHS R21 CA212958NCI NIH HHS R35 CA197588NCI NIH HHS R35 CA197743NCI NIH HHS R35 CA210057NCI NIH HHS R35 CA242379NCI NIH HHS T32 CA009666NCI NIH HHS U54 CA210184NIAID NIH HHS R01 AI047389NIAID NIH HHS R37 AI047389NIDA NIH HHS R03 DA034602NIGMS NIH HHS T32 GM007287NIH HHS DP5 OD026395NIH HHS S10 OD023669
Abstract
A hallmark of metastasis is the adaptation of tumor cells to new environments. Metabolic constraints imposed by the serine and glycine-limited brain environment restrict metastatic tumor growth. How brain metastases overcome these growth-prohibitive conditions is poorly understood. Here, we demonstrate that 3-phosphoglycerate dehydrogenase (PHGDH), which catalyzes the rate-limiting step of glucose-derived serine synthesis, is a major determinant of brain metastasis in multiple human cancer types and preclinical models. Enhanced serine synthesis proved important for nucleotide production and cell proliferation in highly aggressive brain metastatic cells.
Indexed as
AnimalsAntineoplastic AgentsBrainBrain NeoplasmsCell Line, TumorDatasets as TopicDrug Resistance, NeoplasmFemaleGene Knockdown TechniquesGlycineHumansMetabolomicsMicePhosphoglycerate DehydrogenaseProteomicsRNA-SeqAntineoplastic AgentsGlycinePhosphoglycerate DehydrogenaseSerine
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