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Establishment of Tumor Treating Fields Combined With Mild Hyperthermia as Novel Supporting Therapy for Pancreatic Cancer

Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumor with poor prognosis and limited therapeutic options. Alternating electrical fields with low intensity called “Tumor Treating Fields” (TTFields) are a new, non-invasive approach with almost no side effects and phase 3 trials are ongo...

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Autores principales: Bai, Liping, Pfeifer, Tobias, Gross, Wolfgang, De La Torre, Carolina, Zhao, Shuyang, Liu, Li, Schaefer, Michael, Herr, Ingrid
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8597267/
https://www.ncbi.nlm.nih.gov/pubmed/34804927
http://dx.doi.org/10.3389/fonc.2021.738801
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author Bai, Liping
Pfeifer, Tobias
Gross, Wolfgang
De La Torre, Carolina
Zhao, Shuyang
Liu, Li
Schaefer, Michael
Herr, Ingrid
author_facet Bai, Liping
Pfeifer, Tobias
Gross, Wolfgang
De La Torre, Carolina
Zhao, Shuyang
Liu, Li
Schaefer, Michael
Herr, Ingrid
author_sort Bai, Liping
collection PubMed
description Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumor with poor prognosis and limited therapeutic options. Alternating electrical fields with low intensity called “Tumor Treating Fields” (TTFields) are a new, non-invasive approach with almost no side effects and phase 3 trials are ongoing in advanced PDAC. We evaluated TTFields in combination with mild hyperthermia. Three established human PDAC cell lines and an immortalized pancreatic duct cell line were treated with TTFields and hyperthermia at 38.5°C, followed by microscopy, assays for MTT, migration, colony and sphere formation, RT-qPCR, FACS, Western blot, microarray and bioinformatics, and in silico analysis using the online databases GSEA, KEGG, Cytoscape-String, and Kaplan-Meier Plotter. Whereas TTFields and hyperthermia alone had weak effects, their combination strongly inhibited the viability of malignant, but not those of nonmalignant cells. Progression features and the cell cycle were impaired, and autophagy was induced. The identified target genes were key players in autophagy, the cell cycle and DNA repair. The expression profiles of part of these target genes were significantly involved in the survival of PDAC patients. In conclusion, the combination of TTFields with mild hyperthermia results in greater efficacy without increased toxicity and could be easily clinically approved as supporting therapy.
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spelling pubmed-85972672021-11-18 Establishment of Tumor Treating Fields Combined With Mild Hyperthermia as Novel Supporting Therapy for Pancreatic Cancer Bai, Liping Pfeifer, Tobias Gross, Wolfgang De La Torre, Carolina Zhao, Shuyang Liu, Li Schaefer, Michael Herr, Ingrid Front Oncol Oncology Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumor with poor prognosis and limited therapeutic options. Alternating electrical fields with low intensity called “Tumor Treating Fields” (TTFields) are a new, non-invasive approach with almost no side effects and phase 3 trials are ongoing in advanced PDAC. We evaluated TTFields in combination with mild hyperthermia. Three established human PDAC cell lines and an immortalized pancreatic duct cell line were treated with TTFields and hyperthermia at 38.5°C, followed by microscopy, assays for MTT, migration, colony and sphere formation, RT-qPCR, FACS, Western blot, microarray and bioinformatics, and in silico analysis using the online databases GSEA, KEGG, Cytoscape-String, and Kaplan-Meier Plotter. Whereas TTFields and hyperthermia alone had weak effects, their combination strongly inhibited the viability of malignant, but not those of nonmalignant cells. Progression features and the cell cycle were impaired, and autophagy was induced. The identified target genes were key players in autophagy, the cell cycle and DNA repair. The expression profiles of part of these target genes were significantly involved in the survival of PDAC patients. In conclusion, the combination of TTFields with mild hyperthermia results in greater efficacy without increased toxicity and could be easily clinically approved as supporting therapy. Frontiers Media S.A. 2021-11-03 /pmc/articles/PMC8597267/ /pubmed/34804927 http://dx.doi.org/10.3389/fonc.2021.738801 Text en Copyright © 2021 Bai, Pfeifer, Gross, De La Torre, Zhao, Liu, Schaefer and Herr https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Bai, Liping
Pfeifer, Tobias
Gross, Wolfgang
De La Torre, Carolina
Zhao, Shuyang
Liu, Li
Schaefer, Michael
Herr, Ingrid
Establishment of Tumor Treating Fields Combined With Mild Hyperthermia as Novel Supporting Therapy for Pancreatic Cancer
title Establishment of Tumor Treating Fields Combined With Mild Hyperthermia as Novel Supporting Therapy for Pancreatic Cancer
title_full Establishment of Tumor Treating Fields Combined With Mild Hyperthermia as Novel Supporting Therapy for Pancreatic Cancer
title_fullStr Establishment of Tumor Treating Fields Combined With Mild Hyperthermia as Novel Supporting Therapy for Pancreatic Cancer
title_full_unstemmed Establishment of Tumor Treating Fields Combined With Mild Hyperthermia as Novel Supporting Therapy for Pancreatic Cancer
title_short Establishment of Tumor Treating Fields Combined With Mild Hyperthermia as Novel Supporting Therapy for Pancreatic Cancer
title_sort establishment of tumor treating fields combined with mild hyperthermia as novel supporting therapy for pancreatic cancer
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8597267/
https://www.ncbi.nlm.nih.gov/pubmed/34804927
http://dx.doi.org/10.3389/fonc.2021.738801
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