Establishment of Tumor Treating Fields Combined With Mild Hyperthermia as Novel Supporting Therapy for Pancreatic Cancer
| Autor: | Shuyang Zhao, Wolfgang Gross, Tobias Pfeifer, Ingrid Herr, Carolina De La Torre, Li Liu, Liping Bai, Michael Schaefer |
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| Rok vydání: | 2021 |
| Předmět: |
Hyperthermia
Pancreatic duct Cancer Research Microarray business.industry DNA repair Autophagy pancreatic ductal adenocarcinoma Neoplasms. Tumors. Oncology. Including cancer and carcinogens Cell cycle hyperthermia bioinformatics and computational biology medicine.disease alternative therapies tumor treating fields medicine.anatomical_structure Oncology Pancreatic cancer medicine Cancer research KEGG business RC254-282 Original Research |
| Zdroj: | Frontiers in Oncology, Vol 11 (2021) Frontiers in Oncology |
| ISSN: | 2234-943X |
| DOI: | 10.3389/fonc.2021.738801 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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