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Tytuł pozycji:

Prospective experimental treatment of colorectal cancer patients based on organoid drug responses.

Tytuł :
Prospective experimental treatment of colorectal cancer patients based on organoid drug responses.
Autorzy :
Ooft SN; Department of Molecular Oncology and Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands; Oncode Institute, Utrecht, The Netherlands.
Weeber F; Department of Molecular Oncology and Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands; Oncode Institute, Utrecht, The Netherlands.
Schipper L; Department of Molecular Oncology and Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands; Oncode Institute, Utrecht, The Netherlands.
Dijkstra KK; Department of Molecular Oncology and Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands; Oncode Institute, Utrecht, The Netherlands.
McLean CM; Department of Molecular Oncology and Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands; Oncode Institute, Utrecht, The Netherlands.
Kaing S; Department of Molecular Oncology and Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands; Oncode Institute, Utrecht, The Netherlands.
van de Haar J; Department of Molecular Oncology and Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands; Oncode Institute, Utrecht, The Netherlands; Department of Molecular Carcinogenesis, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Prevoo W; Department of Radiology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
van Werkhoven E; Department of Biometrics, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Snaebjornsson P; Department of Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Hoes LR; Department of Molecular Oncology and Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands; Oncode Institute, Utrecht, The Netherlands.
Chalabi M; Department of Molecular Oncology and Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands; Oncode Institute, Utrecht, The Netherlands; Department of Gastrointestinal Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
van der Velden D; Department of Molecular Oncology and Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands; Oncode Institute, Utrecht, The Netherlands; Department of Gastrointestinal Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands; Department of Radiology and Nuclear Medicine, Amsterdam University Medical Center AMC, Amsterdam, The Netherlands.
van Leerdam M; Department of Gastrointestinal Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Boot H; Department of Gastrointestinal Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Grootscholten C; Department of Gastrointestinal Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Huitema ADR; Department of Pharmacy & Pharmacology, The Netherlands Cancer Institute, Amsterdam, The Netherlands; Department of Clinical Pharmacy, University Medical Centre Utrecht, Utrecht, The Netherlands.
Bloemendal HJ; Department of Internal Medicine/Oncology, Radboud University Medical Center Nijmegen, Nijmegen, The Netherlands.
Cuppen E; Oncode Institute, Utrecht, The Netherlands; Division of Biomedical Genetics, Centre for Molecular Medicine, University Medical Centre Utrecht, Utrecht, The Netherlands; Hartwig Medical Foundation, Amsterdam, The Netherlands.
Voest EE; Department of Molecular Oncology and Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands; Oncode Institute, Utrecht, The Netherlands; Department of Gastrointestinal Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands. Electronic address: .
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Źródło :
ESMO open [ESMO Open] 2021 Jun; Vol. 6 (3), pp. 100103. Date of Electronic Publication: 2021 Apr 19.
Typ publikacji :
Journal Article
Język :
English
Imprint Name(s) :
Publication: 2021 : [London] : Elsevier
Original Publication: London : BMJ, [2016]-
Contributed Indexing :
Keywords: clinical trial; colorectal cancer; drug screening; experimental treatment; precision medicine; tumor organoids
Entry Date(s) :
Date Created: 20210422 Latest Revision: 20210621
Update Code :
20210914
PubMed Central ID :
PMC8086019
DOI :
10.1016/j.esmoop.2021.100103
PMID :
33887686
Czasopismo naukowe
Background: Organoid technology has recently emerged as a powerful tool to assess drug sensitivity of individual patient tumors in vitro. Organoids may therefore represent a new avenue for precision medicine, as this circumvents many of the complexities associated with DNA- or transcriptional-profiling.
Materials and Methods: The SENSOR trial was a single-arm, single-center, prospective intervention trial to evaluate the feasibility of patient-derived organoids to allocate patients for treatment with off-label or investigational agents. The primary endpoint was an objective response rate of ≥20%. Patients underwent a biopsy for culture before commencing their last round standard of care. Organoids were exposed to a panel of eight drugs and patients were treated after progression on standard-of-care treatment and when a clear signal of antitumor activity was identified in vitro.
Results: Sixty-one patients were included and we generated 31 organoids of 54 eligible patients. Twenty-five cultures were subjected to drug screening and 19 organoids exhibited substantial responses to one or more drugs. Three patients underwent treatment with vistusertib and three with capivasertib. Despite drug sensitivity of organoids, patients did not demonstrate objective clinical responses to the recommended treatment.
Conclusions: Organoid technology had limited value as a tool for precision medicine in this patient population because a large fraction of patients could not undergo treatment or because the recommended treatment did not elicit an objective response. We identified several essential parameters, such as the culture success rate, clinical deterioration of patients during standard of care, and rational design of drug panels that need to be accounted for in organoid-guided clinical studies.
(Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

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