Clinical Implications of Acquired BRAF Inhibitors Resistance in Melanoma
Understanding the role of mitogen-activated protein kinase (MAPK) pathway-activating mutations in the development and progression of melanoma and their possible use as therapeutic targets has substantially changed the management of this neoplasm, which, until a few years ago, was burdened by severe...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/24/9730 |
| _version_ | 1797544052353138688 |
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| author | Paola Savoia Elisa Zavattaro Ottavio Cremona |
| author_facet | Paola Savoia Elisa Zavattaro Ottavio Cremona |
| author_sort | Paola Savoia |
| collection | DOAJ |
| description | Understanding the role of mitogen-activated protein kinase (MAPK) pathway-activating mutations in the development and progression of melanoma and their possible use as therapeutic targets has substantially changed the management of this neoplasm, which, until a few years ago, was burdened by severe mortality. However, the presence of numerous intrinsic and extrinsic mechanisms of resistance to BRAF inhibitors compromises the treatment responses’ effectiveness and durability. The strategy of overcoming these resistances by combination therapy has proved successful, with the additional benefit of reducing side effects derived from paradoxical activation of the MAPK pathway. Furthermore, the use of other highly specific inhibitors, intermittent dosing schedules and the association of combination therapy with immune checkpoint inhibitors are promising new therapeutic strategies. However, numerous issues related to dose, tolerability and administration sequence still need to be clarified, as is to be expected from currently ongoing trials. In this review, we describe the clinical results of using BRAF inhibitors in advanced melanoma, with a keen interest in strategies aimed at overcoming resistance. |
| first_indexed | 2024-03-10T13:54:04Z |
| format | Article |
| id | doaj.art-384f91f5b91e4e828469f6f70fd3f7a5 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T13:54:04Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-384f91f5b91e4e828469f6f70fd3f7a52023-11-21T01:44:44ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-12-012124973010.3390/ijms21249730Clinical Implications of Acquired BRAF Inhibitors Resistance in MelanomaPaola Savoia0Elisa Zavattaro1Ottavio Cremona2Department of Health Science, University of Eastern Piedmont, Via Solaroli 17, 28100 Novara, ItalyAOU Maggiore della Carità, c.so Mazzini 18, 28100 Novara, ItalyDivision of Neuroscience, San Raffaele Scientific Institute, Università Vita Salute San Raffaele, Via Olgettina 58, 20132 Milano, ItalyUnderstanding the role of mitogen-activated protein kinase (MAPK) pathway-activating mutations in the development and progression of melanoma and their possible use as therapeutic targets has substantially changed the management of this neoplasm, which, until a few years ago, was burdened by severe mortality. However, the presence of numerous intrinsic and extrinsic mechanisms of resistance to BRAF inhibitors compromises the treatment responses’ effectiveness and durability. The strategy of overcoming these resistances by combination therapy has proved successful, with the additional benefit of reducing side effects derived from paradoxical activation of the MAPK pathway. Furthermore, the use of other highly specific inhibitors, intermittent dosing schedules and the association of combination therapy with immune checkpoint inhibitors are promising new therapeutic strategies. However, numerous issues related to dose, tolerability and administration sequence still need to be clarified, as is to be expected from currently ongoing trials. In this review, we describe the clinical results of using BRAF inhibitors in advanced melanoma, with a keen interest in strategies aimed at overcoming resistance.https://www.mdpi.com/1422-0067/21/24/9730metastatic melanomaBRAF inhibitorstarget therapyresistance |
| spellingShingle | Paola Savoia Elisa Zavattaro Ottavio Cremona Clinical Implications of Acquired BRAF Inhibitors Resistance in Melanoma International Journal of Molecular Sciences metastatic melanoma BRAF inhibitors target therapy resistance |
| title | Clinical Implications of Acquired BRAF Inhibitors Resistance in Melanoma |
| title_full | Clinical Implications of Acquired BRAF Inhibitors Resistance in Melanoma |
| title_fullStr | Clinical Implications of Acquired BRAF Inhibitors Resistance in Melanoma |
| title_full_unstemmed | Clinical Implications of Acquired BRAF Inhibitors Resistance in Melanoma |
| title_short | Clinical Implications of Acquired BRAF Inhibitors Resistance in Melanoma |
| title_sort | clinical implications of acquired braf inhibitors resistance in melanoma |
| topic | metastatic melanoma BRAF inhibitors target therapy resistance |
| url | https://www.mdpi.com/1422-0067/21/24/9730 |
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