Functional drug susceptibility testing using single-cell mass predicts treatment outcome in patient-derived cancer neurosphere models.

Antineoplastic Agents, Alkylating / pharmacology Biomarkers, Tumor / genetics Brain Neoplasms / drug therapy Cell Size / drug effects DNA Methylation DNA Modification Methylases / genetics DNA Repair Enzymes / genetics Drug Screening Assays, Antitumor / methods Glioblastoma / drug therapy Humans Models, Biological Neoplasm Grading Promoter Regions, Genetic Retrospective Studies Single-Cell Analysis / methods Survival Rate Temozolomide / pharmacology Tumor Suppressor Proteins / genetics
cancer cell mass cell size functional drug susceptibility testing glioblastoma

Journal

Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691

Informations de publication

Date de publication:
05 10 2021
Historique:
received: 13 01 2021
revised: 17 08 2021
accepted: 10 09 2021
entrez: 5 10 2021
pubmed: 6 10 2021
medline: 17 2 2022
Statut: ppublish

Résumé

Functional precision medicine aims to match individual cancer patients to optimal treatment through ex vivo drug susceptibility testing on patient-derived cells. However, few functional diagnostic assays have been validated against patient outcomes at scale because of limitations of such assays. Here, we describe a high-throughput assay that detects subtle changes in the mass of individual drug-treated cancer cells as a surrogate biomarker for patient treatment response. To validate this approach, we determined ex vivo response to temozolomide in a retrospective cohort of 69 glioblastoma patient-derived neurosphere models with matched patient survival and genomics. Temozolomide-induced changes in cell mass distributions predict patient overall survival similarly to O

Identifiants

DOI: 10.1016/j.celrep.2021.109788 PMID: 34610309
pubmed: 34610309
pii: S2211-1247(21)01247-X
doi: 10.1016/j.celrep.2021.109788
pii:
doi:

Substances chimiques

Antineoplastic Agents, Alkylating 0
Biomarkers, Tumor 0
Tumor Suppressor Proteins 0
DNA Modification Methylases EC 2.1.1.-
MGMT protein, human EC 2.1.1.63
DNA Repair Enzymes EC 6.5.1.-
Temozolomide YF1K15M17Y

Types de publication

Journal Article Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

109788

Subventions

Organisme : NCI NIH HHS
ID : U54 CA217377
Pays : United States
Organisme : NCI NIH HHS
ID : R33 CA191143
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA014051
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA165962
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA219943
Pays : United States

Informations de copyright

Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests S.R.M. and K.L.L. are founders of Travera. S.R.M. is a founder of Affinity Biosensors and an inventor of a relevant patent (US8087284B2). K.L.L. receives consulting fees from BMS, Rarecyte, and Integragen, research funding to DFCI from BMS, Lilly, and Amgen. The other authors declare no competing interests.

Auteurs

Max A Stockslager (MA)

Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA; Koch Institute for Integrative Cancer Research, Cambridge, MA, USA.

Seth Malinowski (S)

Department of Oncologic Pathology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.

Mehdi Touat (M)

Department of Oncologic Pathology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA; Broad Institute of Harvard and MIT, Cambridge, MA, USA; Sorbonne Université, Inserm, CNRS, UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, AP-HP, Hôpitaux Universitaires La Pitié Salpêtrière - Charles Foix, Service de Neurologie 2-Mazarin, Paris, France.

Jennifer C Yoon (JC)

Koch Institute for Integrative Cancer Research, Cambridge, MA, USA.

Jack Geduldig (J)

Department of Oncologic Pathology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.

Mahnoor Mirza (M)

Koch Institute for Integrative Cancer Research, Cambridge, MA, USA.

Annette S Kim (AS)

Department of Pathology, Brigham & Women's Hospital, Harvard Medical School, Boston, MA, USA.

Patrick Y Wen (PY)

Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA USA.

Kin-Hoe Chow (KH)

Center for Patient-Derived Models, Dana-Farber Cancer Institute, Boston, MA, USA.

Keith L Ligon (KL)

Department of Oncologic Pathology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA; Broad Institute of Harvard and MIT, Cambridge, MA, USA; Department of Pathology, Brigham & Women's Hospital, Harvard Medical School, Boston, MA, USA; Center for Patient-Derived Models, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Pathology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: keith_ligon@dfci.harvard.edu.

Scott R Manalis (SR)

Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA; Koch Institute for Integrative Cancer Research, Cambridge, MA, USA; Broad Institute of Harvard and MIT, Cambridge, MA, USA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA. Electronic address: srm@mit.edu.

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Classifications MeSH

questionsmedicales.fr › Actions chimiques et utilisations › Actions toxiques › Noxas › Agents alcoylants › Antinéoplasiques alcoylants › Functional drug susceptibility testing using...
questionsmedicales.fr › Facteurs biologiques › Marqueurs biologiques › Marqueurs biologiques tumoraux › Functional drug susceptibility testing using...
questionsmedicales.fr › Maladies du système nerveux › Tumeurs du système nerveux › Tumeurs du système nerveux central › Tumeurs du cerveau › Functional drug susceptibility testing using...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Taille de la cellule › Functional drug susceptibility testing using...
questionsmedicales.fr › Phénomènes génétiques › Méthylation de l'ADN › Functional drug susceptibility testing using...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Transferases › One-carbon group transferases › Methyltransferases › DNA modification methylases › Functional drug susceptibility testing using...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Enzymes de réparation de l'ADN › Functional drug susceptibility testing using...
questionsmedicales.fr › Techniques d'investigation › Évaluation préclinique de médicament › Tests de criblage d'agents antitumoraux › Functional drug susceptibility testing using...
questionsmedicales.fr › Tumeurs › Tumeurs par type histologique › Tumeurs du tissu nerveux › Tumeurs neuroectodermiques › Tumeurs neuroépitheliales › Gliome › Astrocytome › Glioblastome › Functional drug susceptibility testing using...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Functional drug susceptibility testing using...
questionsmedicales.fr › Techniques d'investigation › Modèles théoriques › Modèles biologiques › Functional drug susceptibility testing using...
questionsmedicales.fr › Diagnostic › Pronostic › Grading des tumeurs › Functional drug susceptibility testing using...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Génome › Composants de génome › Gènes › Composants de gène › Éléments de régulation transcriptionnelle › Régions promotrices (génétique) › Functional drug susceptibility testing using...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études de cohortes › Études rétrospectives › Functional drug susceptibility testing using...
questionsmedicales.fr › Techniques d'investigation › Techniques cytologiques › Analyse sur cellule unique › Functional drug susceptibility testing using...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Collecte de données › Registre civil › Mortalité › Taux de survie › Functional drug susceptibility testing using...
questionsmedicales.fr › Composés hétérocycliques › Composés hétéromonocycliques › Azoles › Imidazoles › Dacarbazine › Témozolomide › Functional drug susceptibility testing using...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines tumorales › Protéines suppresseurs de tumeurs › Functional drug susceptibility testing using...