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EnglishMelanoma is a highly aggressive cancer with the poorest prognosis, representing the dead-liest form of skin cancer. Activating mutations in BRAF are the most frequent genetic alterations, present in approximately 50% of all melanoma cases. The use of specific inhibitors towards mutant BRAF variants and MEK, a downstream signaling target of BRAF in the MAPK pathway, has significantly improved progression-free and overall survival in advanced melanoma patients carrying BRAF mutations. Nevertheless, despite these improvements, resistance still develops within the first year of therapy in around 50% of patients, which is a significant problem in managing BRAF-mutated advanced melanoma. Understanding these mechanisms is one of the mainstreams of the research on BRAFi/MEKi acquired resistance. Both genetic and epigenetic mechanisms have been described. Moreover, in recent years, oxidative stress has emerged as another major force involved in all the phases of melanoma development, from initiation to progression until the onsets of the metastatic phenotype and chemoresistance, and has thus become a target for therapy. In the present review, we discuss the current knowledge on oxidative stress and its signaling in melanoma, as well as the oxidative stress-related mechanisms in the acquired resistance to targeted therapies.
| Titolo: | Oxidative stress-related mechanisms in melanoma and in the acquired resistance to targeted therapies | |
| Autori Riconosciuti: | ||
| Autori: | Pizzimenti S.; Ribero S.; Cucci M.A.; Grattarola M.; Monge C.; Dianzani C.; Barrera G.; Muzio G. | |
| Data di pubblicazione: | 2021 | |
| Abstract: | Melanoma is a highly aggressive cancer with the poorest prognosis, representing the dead-liest form of skin cancer. Activating mutations in BRAF are the most frequent genetic alterations, present in approximately 50% of all melanoma cases. The use of specific inhibitors towards mutant BRAF variants and MEK, a downstream signaling target of BRAF in the MAPK pathway, has significantly improved progression-free and overall survival in advanced melanoma patients carrying BRAF mutations. Nevertheless, despite these improvements, resistance still develops within the first year of therapy in around 50% of patients, which is a significant problem in managing BRAF-mutated advanced melanoma. Understanding these mechanisms is one of the mainstreams of the research on BRAFi/MEKi acquired resistance. Both genetic and epigenetic mechanisms have been described. Moreover, in recent years, oxidative stress has emerged as another major force involved in all the phases of melanoma development, from initiation to progression until the onsets of the metastatic phenotype and chemoresistance, and has thus become a target for therapy. In the present review, we discuss the current knowledge on oxidative stress and its signaling in melanoma, as well as the oxidative stress-related mechanisms in the acquired resistance to targeted therapies. | |
| Volume: | 10 | |
| Fascicolo: | 12 | |
| Pagina iniziale: | 1942 | |
| Pagina finale: | 1971 | |
| Digital Object Identifier (DOI): | 10.3390/antiox10121942 | |
| Parole Chiave: | ALDH; Antioxidants; BRAFi; Lipid peroxidation; MEKi; Melanoma; Nrf2; Oxidative stress; Resistance; RNS; ROS; Targeted therapies | |
| Rivista: | ANTIOXIDANTS | |
| Appare nelle tipologie: | 03B-Review in Rivista / Rassegna della Lett. in Riv. / Nota Critica |
File in questo prodotto:
| File | Descrizione | Tipologia | Licenza | |
|---|---|---|---|---|
| 2021 antioxidants melanoma review.pdf | Articolo | PDF EDITORIALE | Open Access Visualizza/Apri |
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