Mutagenic Consequences of Sublethal Cell Death Signaling
Many human cancers exhibit defects in key DNA damage response elements that can render tumors insensitive to the cell death-promoting properties of DNA-damaging therapies. Using agents that directly induce apoptosis by targeting apoptotic components, rather than relying on DNA damage to indirectly s...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-06-01
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| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/22/11/6144 |
| _version_ | 1797531128190468096 |
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| author | Christine J. Hawkins Mark A. Miles |
| author_facet | Christine J. Hawkins Mark A. Miles |
| author_sort | Christine J. Hawkins |
| collection | DOAJ |
| description | Many human cancers exhibit defects in key DNA damage response elements that can render tumors insensitive to the cell death-promoting properties of DNA-damaging therapies. Using agents that directly induce apoptosis by targeting apoptotic components, rather than relying on DNA damage to indirectly stimulate apoptosis of cancer cells, may overcome classical blocks exploited by cancer cells to evade apoptotic cell death. However, there is increasing evidence that cells surviving sublethal exposure to classical apoptotic signaling may recover with newly acquired genomic changes which may have oncogenic potential, and so could theoretically spur the development of subsequent cancers in cured patients. Encouragingly, cells surviving sublethal necroptotic signaling did not acquire mutations, suggesting that necroptosis-inducing anti-cancer drugs may be less likely to trigger therapy-related cancers. We are yet to develop effective direct inducers of other cell death pathways, and as such, data regarding the consequences of cells surviving sublethal stimulation of those pathways are still emerging. This review details the currently known mutagenic consequences of cells surviving different cell death signaling pathways, with implications for potential oncogenic transformation. Understanding the mechanisms of mutagenesis associated (or not) with various cell death pathways will guide us in the development of future therapeutics to minimize therapy-related side effects associated with DNA damage. |
| first_indexed | 2024-03-10T10:39:34Z |
| format | Article |
| id | doaj.art-f11ef17f35334db59e09a2ba9eff8ef6 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T10:39:34Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-f11ef17f35334db59e09a2ba9eff8ef62023-11-21T23:06:27ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-06-012211614410.3390/ijms22116144Mutagenic Consequences of Sublethal Cell Death SignalingChristine J. Hawkins0Mark A. Miles1Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, VIC 3086, AustraliaDepartment of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, VIC 3086, AustraliaMany human cancers exhibit defects in key DNA damage response elements that can render tumors insensitive to the cell death-promoting properties of DNA-damaging therapies. Using agents that directly induce apoptosis by targeting apoptotic components, rather than relying on DNA damage to indirectly stimulate apoptosis of cancer cells, may overcome classical blocks exploited by cancer cells to evade apoptotic cell death. However, there is increasing evidence that cells surviving sublethal exposure to classical apoptotic signaling may recover with newly acquired genomic changes which may have oncogenic potential, and so could theoretically spur the development of subsequent cancers in cured patients. Encouragingly, cells surviving sublethal necroptotic signaling did not acquire mutations, suggesting that necroptosis-inducing anti-cancer drugs may be less likely to trigger therapy-related cancers. We are yet to develop effective direct inducers of other cell death pathways, and as such, data regarding the consequences of cells surviving sublethal stimulation of those pathways are still emerging. This review details the currently known mutagenic consequences of cells surviving different cell death signaling pathways, with implications for potential oncogenic transformation. Understanding the mechanisms of mutagenesis associated (or not) with various cell death pathways will guide us in the development of future therapeutics to minimize therapy-related side effects associated with DNA damage.https://www.mdpi.com/1422-0067/22/11/6144DNA damageDNA repairmutagenesisapoptosisnecroptosisferroptosis |
| spellingShingle | Christine J. Hawkins Mark A. Miles Mutagenic Consequences of Sublethal Cell Death Signaling International Journal of Molecular Sciences DNA damage DNA repair mutagenesis apoptosis necroptosis ferroptosis |
| title | Mutagenic Consequences of Sublethal Cell Death Signaling |
| title_full | Mutagenic Consequences of Sublethal Cell Death Signaling |
| title_fullStr | Mutagenic Consequences of Sublethal Cell Death Signaling |
| title_full_unstemmed | Mutagenic Consequences of Sublethal Cell Death Signaling |
| title_short | Mutagenic Consequences of Sublethal Cell Death Signaling |
| title_sort | mutagenic consequences of sublethal cell death signaling |
| topic | DNA damage DNA repair mutagenesis apoptosis necroptosis ferroptosis |
| url | https://www.mdpi.com/1422-0067/22/11/6144 |
| work_keys_str_mv | AT christinejhawkins mutagenicconsequencesofsublethalcelldeathsignaling AT markamiles mutagenicconsequencesofsublethalcelldeathsignaling |