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| Content Provider | Springer Nature : BioMed Central |
|---|---|
| Author | Fattore, Luigi Malpicci, Debora Milite, Ciro Castellano, Sabrina Sbardella, Gianluca Botti, Gerardo Ascierto, Paolo A. Mancini, Rita Ciliberto, Gennaro |
| Abstract | Abstract Target therapies based on BRAF and MEK inhibitors (MAPKi) have changed the therapeutic landscape for metastatic melanoma patients bearing mutations in the BRAF kinase. However, the emergence of drug resistance imposes the necessity to conceive novel therapeutic strategies capable to achieve a more durable disease control. In the last years, retrotransposons laying in human genome have been shown to undergo activation during tumorigenesis, where they contribute to genomic instability. Their activation can be efficiently controlled with reverse transcriptase inhibitors (RTIs) frequently used in the treatment of AIDS. These drugs have demonstrated anti-proliferative effects in several cancer models, including also metastatic melanoma. However, to our knowledge no previous study investigated the capability of RTIs to mitigate drug resistance to target therapy in BRAF-mutant melanomas. In this short report we show that the non-nucleoside RTI, SPV122 in combination with MAPKi strongly inhibits BRAF-mutant melanoma cell growth, induces apoptosis, and delays the emergence of resistance to target therapy in vitro. Mechanistically, this combination strongly induces DNA double-strand breaks, mitochondrial membrane depolarization and increased ROS levels. Our results shed further light on the molecular activity of RTI in melanoma and pave the way to their use as a novel therapeutic option to improve the efficacy of target therapy. Video Abstract Graphical abstract |
| Related Links | https://biosignaling.biomedcentral.com/counter/pdf/10.1186/s12964-020-00633-7.pdf |
| Ending Page | 9 |
| Page Count | 9 |
| Starting Page | 1 |
| File Format | HTM / HTML |
| DOI | 10.1186/s12964-020-00633-7 |
| Journal | Cell Communication and Signaling |
| Issue Number | 1 |
| Volume Number | 18 |
| Language | English |
| Publisher | BioMed Central |
| Publisher Date | 2020-09-15 |
| Access Restriction | Open |
| Subject Keyword | Cell Biology Protein-Ligand Interactions Receptors Cytokines and Growth Factors Melanoma Reverse transcriptase inhibitors Target therapy Drug resistance Mitochondrial membrane depolarization DSBs |
| Content Type | Text |
| Resource Type | Article |
| Subject | Biochemistry Cell Biology Molecular Biology |
| Journal Impact Factor | 8.2/2023 |
| 5-Year Journal Impact Factor | 8/2023 |
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