The transcriptomic fingerprint of cancer response to Tumor Treating Fields (TTFields)
Abstract Tumor Treating Fields (TTFields) therapy is an approved cancer treatment modality, based on non-invasive application of electric fields to the tumor region. Proteomic and cell biology methods revealed a versatile mechanism of action to be involved in the response to TTFields. In the current...
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| Main Authors: | , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2025-07-01
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| Series: | Cell Death Discovery |
| Online Access: | https://doi.org/10.1038/s41420-025-02615-5 |
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| author | Kerem Wainer-Katsir Adi Haber Hila Fishman Lianghao Ding Michael D. Story Renfei Du Ulf D. Kahlert Laura Mannarino Federica Mirimao Monica Lupi Maurizio D’Incalci Gitit Lavy-Shahaf Hila Ene Roni Frechtel-Gerzi Zeina Drawshy Antonia Martinez-Conde Eyal Dor-On Yaara Porat Moshe Giladi Uri Weinberg Yoram Palti |
| author_facet | Kerem Wainer-Katsir Adi Haber Hila Fishman Lianghao Ding Michael D. Story Renfei Du Ulf D. Kahlert Laura Mannarino Federica Mirimao Monica Lupi Maurizio D’Incalci Gitit Lavy-Shahaf Hila Ene Roni Frechtel-Gerzi Zeina Drawshy Antonia Martinez-Conde Eyal Dor-On Yaara Porat Moshe Giladi Uri Weinberg Yoram Palti |
| author_sort | Kerem Wainer-Katsir |
| collection | DOAJ |
| description | Abstract Tumor Treating Fields (TTFields) therapy is an approved cancer treatment modality, based on non-invasive application of electric fields to the tumor region. Proteomic and cell biology methods revealed a versatile mechanism of action to be involved in the response to TTFields. In the current research we performed whole transcriptome analysis across tumor types to identify pan-cancer responses to TTFields. For this we collected samples from control and TTFields-treated human cancer cell lines of gastric cancer, pancreatic cancer, ovarian cancer, non-small cell lung carcinoma, pleural mesothelioma, and glioblastoma. The transcriptomic analysis supported previous reported effects: downregulation of pathways associated with cell cycle, cell growth, and proliferation; downregulation of DNA replication and the FA-BRCA DNA repair pathway; and upregulation of cellular responses to stress—senescence, autophagy, and apoptosis. Notably, previously unrecognized downstream effects of TTFields were revealed on cellular metabolism, with downregulation of protein and RNA metabolism, and upregulation of steroid biosynthesis. Additional DNA repair pathways were also found to be downregulated, including nucleotide excision repair, base excision repair, and mismatch repair. In conclusion, this study revealed similar response patterns to TTFields across different tumor types, re-enforcing some already pinpointed mechanisms, while revealing new mechanisms. Unlocking these new mechanisms may allow identification of potential new cancer treatments for application together with TTFields based on mechanistical compatibility. |
| format | Article |
| id | doaj-art-615868c109dd478c9f071dbc080e618c |
| institution | Kabale University |
| issn | 2058-7716 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death Discovery |
| spelling | doaj-art-615868c109dd478c9f071dbc080e618c2025-08-20T04:01:46ZengNature Publishing GroupCell Death Discovery2058-77162025-07-0111111510.1038/s41420-025-02615-5The transcriptomic fingerprint of cancer response to Tumor Treating Fields (TTFields)Kerem Wainer-Katsir0Adi Haber1Hila Fishman2Lianghao Ding3Michael D. Story4Renfei Du5Ulf D. Kahlert6Laura Mannarino7Federica Mirimao8Monica Lupi9Maurizio D’Incalci10Gitit Lavy-Shahaf11Hila Ene12Roni Frechtel-Gerzi13Zeina Drawshy14Antonia Martinez-Conde15Eyal Dor-On16Yaara Porat17Moshe Giladi18Uri Weinberg19Yoram Palti20Novocure LTDNovocure LTDNovocure LTDDepartment of Radiation Oncology, University of Texas Southwestern Medical CenterDepartment of Radiation Oncology, University of Texas Southwestern Medical CenterClinic for Neurosurgery, Heinrich-Heine UniversityMolecular and Experimental Surgery, University Clinic for General-, Visceral-, Vascular- and Trans-Plantation Surgery, Medical Faculty and University Hospital Magdeburg, Otto-von Guericke UniversityLaboratory of Cancer Pharmacology, IRCCS Humanitas Research HospitalDepartment of Oncology, Istituto di Ricerche Farmacologiche Mario Negri IRCCSLaboratory of Cancer Pharmacology, IRCCS Humanitas Research HospitalLaboratory of Cancer Pharmacology, IRCCS Humanitas Research HospitalNovocure LTDNovocure LTDNovocure LTDNovocure LTDNovocure LTDNovocure LTDNovocure LTDNovocure LTDNovocure LTDNovocure LTDAbstract Tumor Treating Fields (TTFields) therapy is an approved cancer treatment modality, based on non-invasive application of electric fields to the tumor region. Proteomic and cell biology methods revealed a versatile mechanism of action to be involved in the response to TTFields. In the current research we performed whole transcriptome analysis across tumor types to identify pan-cancer responses to TTFields. For this we collected samples from control and TTFields-treated human cancer cell lines of gastric cancer, pancreatic cancer, ovarian cancer, non-small cell lung carcinoma, pleural mesothelioma, and glioblastoma. The transcriptomic analysis supported previous reported effects: downregulation of pathways associated with cell cycle, cell growth, and proliferation; downregulation of DNA replication and the FA-BRCA DNA repair pathway; and upregulation of cellular responses to stress—senescence, autophagy, and apoptosis. Notably, previously unrecognized downstream effects of TTFields were revealed on cellular metabolism, with downregulation of protein and RNA metabolism, and upregulation of steroid biosynthesis. Additional DNA repair pathways were also found to be downregulated, including nucleotide excision repair, base excision repair, and mismatch repair. In conclusion, this study revealed similar response patterns to TTFields across different tumor types, re-enforcing some already pinpointed mechanisms, while revealing new mechanisms. Unlocking these new mechanisms may allow identification of potential new cancer treatments for application together with TTFields based on mechanistical compatibility.https://doi.org/10.1038/s41420-025-02615-5 |
| spellingShingle | Kerem Wainer-Katsir Adi Haber Hila Fishman Lianghao Ding Michael D. Story Renfei Du Ulf D. Kahlert Laura Mannarino Federica Mirimao Monica Lupi Maurizio D’Incalci Gitit Lavy-Shahaf Hila Ene Roni Frechtel-Gerzi Zeina Drawshy Antonia Martinez-Conde Eyal Dor-On Yaara Porat Moshe Giladi Uri Weinberg Yoram Palti The transcriptomic fingerprint of cancer response to Tumor Treating Fields (TTFields) Cell Death Discovery |
| title | The transcriptomic fingerprint of cancer response to Tumor Treating Fields (TTFields) |
| title_full | The transcriptomic fingerprint of cancer response to Tumor Treating Fields (TTFields) |
| title_fullStr | The transcriptomic fingerprint of cancer response to Tumor Treating Fields (TTFields) |
| title_full_unstemmed | The transcriptomic fingerprint of cancer response to Tumor Treating Fields (TTFields) |
| title_short | The transcriptomic fingerprint of cancer response to Tumor Treating Fields (TTFields) |
| title_sort | transcriptomic fingerprint of cancer response to tumor treating fields ttfields |
| url | https://doi.org/10.1038/s41420-025-02615-5 |
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