NOTCH3 missense mutations as predictor of long-term response to gemcitabine in a patient with epithelioid hemangioendothelioma.


Journal

Journal of cancer research and clinical oncology
ISSN: 1432-1335
Titre abrégé: J Cancer Res Clin Oncol
Pays: Germany
ID NLM: 7902060

Informations de publication

Date de publication:
Aug 2023
Historique:
received: 05 01 2023
accepted: 24 01 2023
medline: 24 7 2023
pubmed: 8 2 2023
entrez: 7 2 2023
Statut: ppublish

Résumé

Epithelioid hemangioendothelioma (EHE) as a very rare malignant vascular tumor belongs to the heterogenous group of soft-tissue sarcomas. Depending on the clinical course of the disease, interdisciplinary treatment concepts are required, including surgery, radiotherapy and systemic cancer therapy. However, due to its uncommonness, standard treatment options are lacking so far, especially in advanced disease with distant metastases. Here we report on an unusual case of a patient with metastasized EHE showing long-term response to second line treatment with gemcitabine over almost 2 decades. Cancer genome sequencing of the patient's tumor tissue detected a NOTCH3 missense mutation which could provide an explanation for these clinical findings. NOTCH3 is known to be a mediator of resistance towards gemcitabine-based cancer treatment, at least in pancreatic cancer and non-small cell lung cancer. The observation that this missense mutation of NOTCH3 is associated with an increased response to treatment with gemcitabine in EHE can be used prospectively to assess NOTCH3 as potential biomarker for predicting therapy response to gemcitabine.

Identifiants

pubmed: 36749424
doi: 10.1007/s00432-023-04598-1
pii: 10.1007/s00432-023-04598-1
pmc: PMC10356887
doi:

Substances chimiques

Gemcitabine 0
NOTCH3 protein, human 0
Receptor, Notch3 0

Types de publication

Case Reports Journal Article Review

Langues

eng

Sous-ensembles de citation

IM

Pagination

6753-6757

Subventions

Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States

Informations de copyright

© 2023. The Author(s).

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Auteurs

Moritz Schmidt (M)

Department of Medical Oncology and Pneumology (Internal Medicine VIII), University Hospital Tuebingen, 72076, Tuebingen, Germany.
DFG Cluster of Excellence 2180 'Image-Guided and Functional Instructed Tumor Therapy' (iFIT), University of Tuebingen, 72076, Tuebingen, Germany.

Sven Mattern (S)

Department of Pathology, University Hospital Tuebingen, Tuebingen, Germany.

Stephan Singer (S)

Department of Pathology, University Hospital Tuebingen, Tuebingen, Germany.

Martin Schulze (M)

Praxis Für Humangenetik Tübingen, Tuebingen, Germany.

Saskia Biskup (S)

Praxis Für Humangenetik Tübingen, Tuebingen, Germany.
CeGaT GmbH, Center for Genomics and Transcriptomics, Tuebingen, Germany.

Patrick Krumm (P)

Department of Radiology, University Hospital Tuebingen, Tuebingen, Germany.

Ulrich M Lauer (UM)

Department of Medical Oncology and Pneumology (Internal Medicine VIII), University Hospital Tuebingen, 72076, Tuebingen, Germany.
DFG Cluster of Excellence 2180 'Image-Guided and Functional Instructed Tumor Therapy' (iFIT), University of Tuebingen, 72076, Tuebingen, Germany.
German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Tuebingen, Germany.

Lars Zender (L)

Department of Medical Oncology and Pneumology (Internal Medicine VIII), University Hospital Tuebingen, 72076, Tuebingen, Germany.
DFG Cluster of Excellence 2180 'Image-Guided and Functional Instructed Tumor Therapy' (iFIT), University of Tuebingen, 72076, Tuebingen, Germany.
German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Tuebingen, Germany.

Clemens Hinterleitner (C)

Department of Medical Oncology and Pneumology (Internal Medicine VIII), University Hospital Tuebingen, 72076, Tuebingen, Germany.
DFG Cluster of Excellence 2180 'Image-Guided and Functional Instructed Tumor Therapy' (iFIT), University of Tuebingen, 72076, Tuebingen, Germany.
Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Martina Hinterleitner (M)

Department of Medical Oncology and Pneumology (Internal Medicine VIII), University Hospital Tuebingen, 72076, Tuebingen, Germany. martina.hinterleitner@med.uni-tuebingen.de.
DFG Cluster of Excellence 2180 'Image-Guided and Functional Instructed Tumor Therapy' (iFIT), University of Tuebingen, 72076, Tuebingen, Germany. martina.hinterleitner@med.uni-tuebingen.de.

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Classifications MeSH