ArticleScience (New York, N.Y.)2020
Partitioning of cancer therapeutics in nuclear condensates.
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Article in Science (New York, N.Y.), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 316 papers.
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316citing papers in PubMed
23.9field-weighted citation impact, top 1% of its field
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316 citing papers in PubMed, 510 citations in OpenAlex.
- Recent advances in coarse-grained simulations of nucleic acid condensation.The Biochemical journal · 2026Review
- High-throughput identification of endogenous biomolecular condensates and phase-separating proteins.Nature protocols · 2026Review
- Condensates in fusion oncoprotein-driven leukemia: new biology and therapeutic opportunities.Trends in cancer · 2026Review
- Drug delivery gets subcellular.Nature · 2026Article
- Beyond the canonical view: steroid receptor network plasticity and mechanosensitive chromatin integration in breast cancer.NAR cancer · 2026Review
- Biomolecular condensates can function as inherent catalysts.Molecular cell · 2026Article
- Exclusion of RNA-binding domains from G-quadruplex condensates by G-quadruplex ligands.RSC chemical biology · 2026Article
- The emerging synergy of experimental and computational approaches for therapeutic modulation of biomolecular condensates.SLAS discovery : advancing life sciences R & D · 2026Review
- Hiding in Plain Sight: HIV-1 Membraneless Organelles as Nuclear Hubs-Host Hijacking, Replication, Immune Evasion, and Drug-Access Implications.Pathogens (Basel, Switzerland) · 2026Review
- Active RNA synthesis patterns nuclear condensates.Cell systems · 2026Article
- TEAD1 condensates are transcriptionally inactive storage sites on the pericentromeric heterochromatin in cancer cells.Nature cell biology · 2026Article
- amyloid-predict and LLPS-predict: Predicting phase separation propensities in the intrinsically disordered proteome.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Learning molecular determinants of selective small-molecule partitioning across biomolecular condensates.bioRxiv : the preprint server for biology · 2026Article
- Disrupting SOX2 self-association and condensate formation to overcome chemotherapeutic drug resistance in lung squamous cell carcinoma.Signal transduction and targeted therapy · 2026Article
- Small molecules modulate the biomolecular condensates and liquid‒liquid phase separation.Acta pharmaceutica Sinica. B · 2026Review
- How intrinsically disordered regions shape the function of CREB-binding protein.Biochemical Society transactions · 2026Review
- EBF2 condensates enable adipose thermogenesis through ZFP423 sequestration and epigenetic remodeling.Nature communications · 2026Article
- Navigating condensate micropolarity to enhance small-molecule drug targeting.Nature chemical biology · 2026Article
- Proteasomal control of transcription factors: mechanisms, regulation and dysregulation.Cellular and molecular life sciences : CMLS · 2026Review
- Tuning mechanical softness as a design principle in drug delivery: A biomechanical perspective.Acta pharmaceutica Sinica. B · 2026Review
256 more citing papers are in PubMed but not listed here.
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Authors and funding
32 authors at 9 institutions in 3 countries.
Isaac A Klein *Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.ORCID 0000-0002-6032-239X
Ann Boija *Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.ORCID 0000-0003-4659-9154
Lena K AfeyanWhitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
Susana Wilson HawkenWhitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
Mengyang FanDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.ORCID 0000-0002-0871-8792
Alessandra Dall'AgneseWhitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.ORCID 0000-0001-9654-371X
Ozgur OksuzWhitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.ORCID 0000-0001-8393-8501
Jonathan E HenningerWhitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.ORCID 0000-0002-9604-2007
Krishna ShrinivasDepartment of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.ORCID 0000-0002-4167-9385
Benjamin R SabariWhitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.ORCID 0000-0002-6411-3907
Ido SagiWhitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.ORCID 0000-0003-0527-2710
Victoria E ClarkWhitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.ORCID 0000-0002-6781-9980
Jesse M PlattWhitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
Mrityunjoy KarMax Planck Institute for the Physics of Complex Systems, 01187 Dresden, Germany.ORCID 0000-0002-7910-9580
Patrick M McCallMax Planck Institute for the Physics of Complex Systems, 01187 Dresden, Germany.ORCID 0000-0002-6623-4673
Alicia V ZamudioWhitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
John C ManteigaWhitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.ORCID 0000-0002-0385-6176
Eliot L CoffeyWhitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
Charles H LiWhitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.ORCID 0000-0001-8091-6112
Nancy M HannettWhitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
Yang Eric GuoWhitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
Tim-Michael DeckerDepartment of Biochemistry, University of Colorado, Boulder, CO 80303, USA.ORCID 0000-0001-8343-6579
Tong Ihn LeeWhitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.ORCID 0000-0003-1847-0898
Tinghu ZhangDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Jing-Ke WengWhitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.ORCID 0000-0003-3059-0075
Dylan J TaatjesDepartment of Biochemistry, University of Colorado, Boulder, CO 80303, USA.
Arup ChakrabortyDepartment of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.ORCID 0000-0003-1268-9602
Phillip A SharpDepartment of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.ORCID 0000-0003-1465-1691
Young Tae ChangDepartment of Chemistry, Pohang University of Science and Technology, and Center for Self-assembly and Complexity, Institute for Basic Science (IBS), Pohang 37673, Republic of Korea.ORCID 0000-0002-1927-3688
Anthony A HymanMax Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany.ORCID 0000-0003-3664-154X
Nathanael S GrayDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.ORCID 0000-0001-5354-7403
Richard A YoungWhitehead Institute for Biomedical Research, Cambridge, MA 02142, USA. young@wi.mit.edu.ORCID 0000-0001-8855-8647
Whitehead Institute for Biomedical Research · USHarvard University · USMassachusetts Institute of Technology · USMax Planck Institute for the Physics of Complex Systems · DEUniversity of Colorado Boulder · USInstitute for Basic Science · KRMassachusetts General Hospital · USMax Planck Institute of Molecular Cell Biology and Genetics · DERagon Institute of MGH, MIT and Harvard · US
Funding
PRE-DOCTORAL TRAINING IN THE BIOLOGICAL SCIENCEST32GM007287 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI BELL, STEPHEN P., KEATING, AMY E · 1985 to 2019
$40.8MTargeting Genomic Instability and Evolution in MyelomaP01CA155258 · NCI · DANA-FARBER CANCER INST · PI Jill Corre · 2011 to 2026
$32.5MTranscriptional Regulatory Networks in Living CellsR01HG002668 · NHGRI · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · PI YOUNG, RICHARD · 2003 to 2016
$17.9MRESEARCH TRAINING IN DIGESTIVE DISEASES AND NUTRITIONT32DK007191 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI RAYMOND T CHUNG · 1986 to 2026
$14.6MREGULATION OF MRNA PROCESSINGR01GM034277 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI SHARP, PHILLIP A · 1985 to 2021
$8.0MGraduate Training in Computational and Systems BiologyT32GM087237 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI BURGE, CHRISTOPHER B · 2009 to 2023
$4.6MTranscriptional regulatory networks in living cellsR01GM123511 · NIGMS · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · PI YOUNG, RICHARD · 2017 to 2020
$3.6MTargeting the transcriptional and epigenetic landscape in chemo-refractory Small-Cell Lung CancerU01CA213333 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI GRAY, NATHANAEL SCHIANDER, WONG, KWOK KIN · 2017 to 2021
$3.3MMediator Kinases and Transcription RegulationR01GM117370 · NIGMS · UNIVERSITY OF COLORADO · PI TAATJES, DYLAN J · 2016 to 2019
$1.5MNCI NIH HHS P01 CA155258NCI NIH HHS U01 CA213333NHGRI NIH HHS R01 HG002668NIDDK NIH HHS T32 DK007191NIGMS NIH HHS R01 GM034277NIGMS NIH HHS R01 GM117370NIGMS NIH HHS R01 GM123511NIGMS NIH HHS T32 GM007287NIGMS NIH HHS T32 GM087237
Abstract
The nucleus contains diverse phase-separated condensates that compartmentalize and concentrate biomolecules with distinct physicochemical properties. Here, we investigated whether condensates concentrate small-molecule cancer therapeutics such that their pharmacodynamic properties are altered. We found that antineoplastic drugs become concentrated in specific protein condensates in vitro and that this occurs through physicochemical properties independent of the drug target. This behavior was also observed in tumor cells, where drug partitioning influenced drug activity. Altering the properties of the condensate was found to affect the concentration and activity of drugs. These results suggest that selective partitioning and concentration of small molecules within condensates contributes to drug pharmacodynamics and that further understanding of this phenomenon may facilitate advances in disease therapy.
Indexed as
Drug Resistance, NeoplasmAntineoplastic AgentsBromodomain Containing ProteinsCell Cycle ProteinsCell NucleusChromobox Protein Homolog 5Chromosomal Proteins, Non-HistoneGreen Fluorescent ProteinsHumansMediator Complex Subunit 1NeoplasmsNuclear ProteinsNucleophosminRecombinant ProteinsSerine-Arginine Splicing FactorsTranscription FactorsAntineoplastic AgentsBRD4 protein, humanBromodomain Containing ProteinsCell Cycle ProteinsChromobox Protein Homolog 5Chromosomal Proteins, Non-HistoneGreen Fluorescent ProteinsMED1 protein, humanMediator Complex Subunit 1Nuclear ProteinsNucleophosminRecombinant ProteinsSerine-Arginine Splicing FactorsSRSF2 protein, humanTranscription Factors
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