Patient-derived organoids as a platform for modeling a patient's response to chemoradiotherapy in esophageal cancer.


Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
29 10 2021
Historique:
received: 27 05 2021
accepted: 08 10 2021
entrez: 30 10 2021
pubmed: 31 10 2021
medline: 1 2 2022
Statut: epublish

Résumé

3D patient-derived organoids (PDOs) have been utilized to evaluate potential therapies for patients with different cancers. However, the use of PDOs created from treatment-naive patient biopsies for prediction of clinical outcomes in patients with esophageal cancer has not yet been reported. Herein we describe a pilot prospective observational study with the goal of determining whether esophageal cancer PDOs created from treatment naive patients can model or predict clinical outcomes. Endoscopic biopsies of treatment-naive patients at a single tertiary care center were used to generate esophageal cancer PDOs, which were treated with standard-of-care chemotherapy, gamma-irradiation, and newer non-standard approaches, such as proton beam therapy or two small molecule inhibitors. Clinical outcomes of patients following neoadjuvant treatment were compared to their in vitro PDO responses, demonstrating the PDO's ability to mirror clinical response, suggesting the value of PDOs in prediction of clinical response to new therapeutic approaches. Future prospective clinical trials should test the use of pre-treatment PDOs to identify specific, targeted therapies for individual patients with esophageal adenocarcinoma.

Identifiants

pubmed: 34716381
doi: 10.1038/s41598-021-00706-8
pii: 10.1038/s41598-021-00706-8
pmc: PMC8556341
doi:

Substances chimiques

Antineoplastic Agents 0

Types de publication

Journal Article Observational Study Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

21304

Subventions

Organisme : NIDDK NIH HHS
ID : R03DK118310
Pays : United States
Organisme : NIDDK NIH HHS
ID : R03 DK118310
Pays : United States
Organisme : NIEHS NIH HHS
ID : P30 ES013508
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA098101
Pays : United States
Organisme : NIEHS NIH HHS
ID : P30ES013508
Pays : United States
Organisme : NCI NIH HHS
ID : P01CA098101
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30DK050306
Pays : United States
Organisme : NCI NIH HHS
ID : U54CA63004
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK124266
Pays : United States
Organisme : NCI NIH HHS
ID : F32 CA221094
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK050306
Pays : United States
Organisme : NCI NIH HHS
ID : K99 CA252153
Pays : United States

Informations de copyright

© 2021. The Author(s).

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Auteurs

Tatiana A Karakasheva (TA)

Division of Gastroenterology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Gastrointestinal Epithelium Modeling Program, Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Philadelphia, Philadelphia, PA, USA.

Joel T Gabre (JT)

Division of Gastroenterology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Division of Digestive and Liver Diseases, Department of Medicine and Herbert Irving Comprehensive Cancer Research Center, Columbia University Irving Medical Center, 1130 St. Nicholas Avenue, Suite 201, New York, NY, 10032, USA.

Uma M Sachdeva (UM)

Division of Thoracic Surgery, Massachusetts General Hospital, Boston, MA, USA.

Ricardo Cruz-Acuña (R)

Division of Gastroenterology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Herbert Irving Comprehensive Cancer Research Center, Columbia University Irving Medical Center, New York, NY, USA.

Eric W Lin (EW)

Division of Gastroenterology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Massachusetts General Hospital, Boston, MA, USA.

Maureen DeMarshall (M)

Division of Gastroenterology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Gary W Falk (GW)

Division of Gastroenterology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Gregory G Ginsberg (GG)

Division of Gastroenterology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Zhaohai Yang (Z)

Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Michele M Kim (MM)

Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Eric S Diffenderfer (ES)

Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Jason R Pitarresi (JR)

Division of Gastroenterology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Jinyang Li (J)

Division of Gastroenterology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Amanda B Muir (AB)

Gastrointestinal Epithelium Modeling Program, Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Philadelphia, Philadelphia, PA, USA.

Kathryn E Hamilton (KE)

Gastrointestinal Epithelium Modeling Program, Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Philadelphia, Philadelphia, PA, USA.

Hiroshi Nakagawa (H)

Division of Digestive and Liver Diseases, Department of Medicine and Herbert Irving Comprehensive Cancer Research Center, Columbia University Irving Medical Center, 1130 St. Nicholas Avenue, Suite 201, New York, NY, 10032, USA.

Adam J Bass (AJ)

Dana-Farber Cancer Institute, Harvard Medical School, Broad Institute, Boston, MA, USA.
Herbert Irving Comprehensive Cancer Research Center, Columbia University Irving Medical Center, New York, NY, USA.

Anil K Rustgi (AK)

Division of Digestive and Liver Diseases, Department of Medicine and Herbert Irving Comprehensive Cancer Research Center, Columbia University Irving Medical Center, 1130 St. Nicholas Avenue, Suite 201, New York, NY, 10032, USA. akr2164@cumc.columbia.edu.

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