Hacking the Lipidome: New Ferroptosis Strategies in Cancer Therapy
The concept of redirecting metabolic pathways in cancer cells for therapeutic purposes has become a prominent theme in recent research. Now, with the advent of ferroptosis, a new chink in the armor has evolved that allows for repurposing of ferroptosis-sensitive lipids in order to trigger cell death...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2024-02-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/12/3/541 |
| _version_ | 1797241944937594880 |
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| author | Borys Varynskyi Joel A. Schick |
| author_facet | Borys Varynskyi Joel A. Schick |
| author_sort | Borys Varynskyi |
| collection | DOAJ |
| description | The concept of redirecting metabolic pathways in cancer cells for therapeutic purposes has become a prominent theme in recent research. Now, with the advent of ferroptosis, a new chink in the armor has evolved that allows for repurposing of ferroptosis-sensitive lipids in order to trigger cell death. This review presents the historical context of lipidomic and metabolic alterations in cancer cells associated with ferroptosis sensitization. The main proferroptotic genes and pathways are identified as therapeutic targets for increasing susceptibility to ferroptosis. In this review, a particular emphasis is given to pathways in cancer cells such as de novo lipogenesis, which has been described as a potential target for ferroptosis sensitization. Additionally, we propose a connection between ketolysis inhibition and sensitivity to ferroptosis as a new vulnerability in cancer cells. The main proferroptotic genes and pathways have been identified as therapeutic targets for increasing susceptibility to ferroptosis. Proferroptotic metabolic pathways and vulnerable points, along with suggested agonists or antagonists, are also discussed. Finally, general therapeutic strategies for ferroptosis sensitization based on the manipulation of the lipidome in ferroptosis-resistant cancer cell lines are proposed. |
| first_indexed | 2024-04-24T18:31:23Z |
| format | Article |
| id | doaj.art-89d53f8f6cec4cf88ff11c6c61cce439 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-04-24T18:31:23Z |
| publishDate | 2024-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-89d53f8f6cec4cf88ff11c6c61cce4392024-03-27T13:22:45ZengMDPI AGBiomedicines2227-90592024-02-0112354110.3390/biomedicines12030541Hacking the Lipidome: New Ferroptosis Strategies in Cancer TherapyBorys Varynskyi0Joel A. Schick1Genetics and Cellular Engineering Group, Research Unit Signaling and Translation, Helmholtz Zentrum Munich, Ingolstädter Landstr. 1, 85764 Neuherberg, GermanyGenetics and Cellular Engineering Group, Research Unit Signaling and Translation, Helmholtz Zentrum Munich, Ingolstädter Landstr. 1, 85764 Neuherberg, GermanyThe concept of redirecting metabolic pathways in cancer cells for therapeutic purposes has become a prominent theme in recent research. Now, with the advent of ferroptosis, a new chink in the armor has evolved that allows for repurposing of ferroptosis-sensitive lipids in order to trigger cell death. This review presents the historical context of lipidomic and metabolic alterations in cancer cells associated with ferroptosis sensitization. The main proferroptotic genes and pathways are identified as therapeutic targets for increasing susceptibility to ferroptosis. In this review, a particular emphasis is given to pathways in cancer cells such as de novo lipogenesis, which has been described as a potential target for ferroptosis sensitization. Additionally, we propose a connection between ketolysis inhibition and sensitivity to ferroptosis as a new vulnerability in cancer cells. The main proferroptotic genes and pathways have been identified as therapeutic targets for increasing susceptibility to ferroptosis. Proferroptotic metabolic pathways and vulnerable points, along with suggested agonists or antagonists, are also discussed. Finally, general therapeutic strategies for ferroptosis sensitization based on the manipulation of the lipidome in ferroptosis-resistant cancer cell lines are proposed.https://www.mdpi.com/2227-9059/12/3/541ferroptosiscancer cellsde novo lipogenesisketolysislipidomicsmetabolic reprogramming |
| spellingShingle | Borys Varynskyi Joel A. Schick Hacking the Lipidome: New Ferroptosis Strategies in Cancer Therapy Biomedicines ferroptosis cancer cells de novo lipogenesis ketolysis lipidomics metabolic reprogramming |
| title | Hacking the Lipidome: New Ferroptosis Strategies in Cancer Therapy |
| title_full | Hacking the Lipidome: New Ferroptosis Strategies in Cancer Therapy |
| title_fullStr | Hacking the Lipidome: New Ferroptosis Strategies in Cancer Therapy |
| title_full_unstemmed | Hacking the Lipidome: New Ferroptosis Strategies in Cancer Therapy |
| title_short | Hacking the Lipidome: New Ferroptosis Strategies in Cancer Therapy |
| title_sort | hacking the lipidome new ferroptosis strategies in cancer therapy |
| topic | ferroptosis cancer cells de novo lipogenesis ketolysis lipidomics metabolic reprogramming |
| url | https://www.mdpi.com/2227-9059/12/3/541 |
| work_keys_str_mv | AT borysvarynskyi hackingthelipidomenewferroptosisstrategiesincancertherapy AT joelaschick hackingthelipidomenewferroptosisstrategiesincancertherapy |