Targeting mitochondria: a novel approach for treating platinum-resistant ovarian cancer
Abstract Ovarian cancer is a prevalent gynecologic malignancy with the second-highest mortality rate among gynecologic malignancies. Platinum-based chemotherapy is the first-line treatment for ovarian cancer; however, a majority of patients with ovarian cancer experience relapse and develop platinum...
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| Language: | English |
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BMC
2024-10-01
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| Series: | Journal of Translational Medicine |
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| Online Access: | https://doi.org/10.1186/s12967-024-05770-y |
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| author | Xin Cui Juan Xu Xuemei Jia |
| author_facet | Xin Cui Juan Xu Xuemei Jia |
| author_sort | Xin Cui |
| collection | DOAJ |
| description | Abstract Ovarian cancer is a prevalent gynecologic malignancy with the second-highest mortality rate among gynecologic malignancies. Platinum-based chemotherapy is the first-line treatment for ovarian cancer; however, a majority of patients with ovarian cancer experience relapse and develop platinum resistance following initial treatment. Despite extensive research on the mechanisms of platinum resistance at the nuclear level, the issue of platinum resistance in ovarian cancer remains largely unresolved. It is noteworthy that mitochondrial DNA (mtDNA) exhibits higher affinity for platinum compared to nuclear DNA (nDNA). Mutations in mtDNA can modulate tumor chemosensitivity through various mechanisms, including DNA damage responses, shifts in energy metabolism, maintenance of Reactive Oxygen Species (ROS) homeostasis, and alterations in mitochondrial dynamics. Concurrently, retrograde signals produced by mtDNA mutations and their subsequent cascades establish communication with the nucleus, leading to the reorganization of the nuclear transcriptome and governing the transcription of genes and signaling pathways associated with chemoresistance. Furthermore, mitochondrial translocation among cells emerges as a crucial factor influencing the effectiveness of chemotherapy in ovarian cancer. This review aims to explore the role and mechanism of mitochondria in platinum resistance, with a specific focus on mtDNA mutations and the resulting metabolic reprogramming, ROS regulation, changes in mitochondrial dynamics, mitochondria-nucleus communication, and mitochondrial transfer. Graphical Abstract |
| format | Article |
| id | doaj-art-09ccba3ab5df4312bf4e8ca9a78b9b68 |
| institution | OA Journals |
| issn | 1479-5876 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj-art-09ccba3ab5df4312bf4e8ca9a78b9b682025-08-20T02:11:50ZengBMCJournal of Translational Medicine1479-58762024-10-0122111310.1186/s12967-024-05770-yTargeting mitochondria: a novel approach for treating platinum-resistant ovarian cancerXin Cui0Juan Xu1Xuemei Jia2Nanjing Women and Children’s Healthcare Hospital, Women’s Hospital of Nanjing Medical UniversityNanjing Women and Children’s Healthcare Hospital, Women’s Hospital of Nanjing Medical UniversityNanjing Women and Children’s Healthcare Hospital, Women’s Hospital of Nanjing Medical UniversityAbstract Ovarian cancer is a prevalent gynecologic malignancy with the second-highest mortality rate among gynecologic malignancies. Platinum-based chemotherapy is the first-line treatment for ovarian cancer; however, a majority of patients with ovarian cancer experience relapse and develop platinum resistance following initial treatment. Despite extensive research on the mechanisms of platinum resistance at the nuclear level, the issue of platinum resistance in ovarian cancer remains largely unresolved. It is noteworthy that mitochondrial DNA (mtDNA) exhibits higher affinity for platinum compared to nuclear DNA (nDNA). Mutations in mtDNA can modulate tumor chemosensitivity through various mechanisms, including DNA damage responses, shifts in energy metabolism, maintenance of Reactive Oxygen Species (ROS) homeostasis, and alterations in mitochondrial dynamics. Concurrently, retrograde signals produced by mtDNA mutations and their subsequent cascades establish communication with the nucleus, leading to the reorganization of the nuclear transcriptome and governing the transcription of genes and signaling pathways associated with chemoresistance. Furthermore, mitochondrial translocation among cells emerges as a crucial factor influencing the effectiveness of chemotherapy in ovarian cancer. This review aims to explore the role and mechanism of mitochondria in platinum resistance, with a specific focus on mtDNA mutations and the resulting metabolic reprogramming, ROS regulation, changes in mitochondrial dynamics, mitochondria-nucleus communication, and mitochondrial transfer. Graphical Abstracthttps://doi.org/10.1186/s12967-024-05770-yMitochondriaPlatinum resistanceMitochondria DNA (mtDNA)Metabolic reprogrammingMitochondrial dynamicsMitochondria-nucleus communication |
| spellingShingle | Xin Cui Juan Xu Xuemei Jia Targeting mitochondria: a novel approach for treating platinum-resistant ovarian cancer Journal of Translational Medicine Mitochondria Platinum resistance Mitochondria DNA (mtDNA) Metabolic reprogramming Mitochondrial dynamics Mitochondria-nucleus communication |
| title | Targeting mitochondria: a novel approach for treating platinum-resistant ovarian cancer |
| title_full | Targeting mitochondria: a novel approach for treating platinum-resistant ovarian cancer |
| title_fullStr | Targeting mitochondria: a novel approach for treating platinum-resistant ovarian cancer |
| title_full_unstemmed | Targeting mitochondria: a novel approach for treating platinum-resistant ovarian cancer |
| title_short | Targeting mitochondria: a novel approach for treating platinum-resistant ovarian cancer |
| title_sort | targeting mitochondria a novel approach for treating platinum resistant ovarian cancer |
| topic | Mitochondria Platinum resistance Mitochondria DNA (mtDNA) Metabolic reprogramming Mitochondrial dynamics Mitochondria-nucleus communication |
| url | https://doi.org/10.1186/s12967-024-05770-y |
| work_keys_str_mv | AT xincui targetingmitochondriaanovelapproachfortreatingplatinumresistantovariancancer AT juanxu targetingmitochondriaanovelapproachfortreatingplatinumresistantovariancancer AT xuemeijia targetingmitochondriaanovelapproachfortreatingplatinumresistantovariancancer |