Braf-Mutant Melanomas: Biology and Therapy
The incidence of melanoma, the most lethal form of skin cancer, has increased mainly due to ultraviolet exposure. The molecular characterization of melanomas has shown a high mutational burden led to the identification of some recurrent genetic alterations. <i>BRAF</i> gene is mutated in...
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MDPI AG
2024-12-01
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| Series: | Current Oncology |
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| Online Access: | https://www.mdpi.com/1718-7729/31/12/568 |
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| author | Elvira Pelosi Germana Castelli Ugo Testa |
| author_facet | Elvira Pelosi Germana Castelli Ugo Testa |
| author_sort | Elvira Pelosi |
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| description | The incidence of melanoma, the most lethal form of skin cancer, has increased mainly due to ultraviolet exposure. The molecular characterization of melanomas has shown a high mutational burden led to the identification of some recurrent genetic alterations. <i>BRAF</i> gene is mutated in 40–50% of melanomas and its role in melanoma development is paramount. <i>BRAF</i> mutations confer constitutive activation of MAPK signalling. The large majority (about 90%) of <i>BRAF</i> mutations occur at amino acid 600; the majority are <i>BRAF<sup>V600E</sup></i> mutations and less frequently <i>BRAF<sup>v600K, V600D</sup></i> and <i><sup>V600M</sup></i>. The introduction of drugs that directly target <i>BRAF</i>-mutant <i>protein (BRAF inhibitors)</i> and of agents that stimulate immune response through targeting of immune check inhibitor consistently improved the survival of melanoma <i>BRAF<sup>V600</sup></i>-mutant patients with unresectable/metastatic disease. In parallel, studies in melanoma stage II-III patients with resectable disease have shown that adjuvant therapy with ICIs and/or targeted therapy improves PFS and RFS, but not OS compared to placebo; however, neoadjuvant therapy plus adjuvant therapy improved therapeutic response compared to adjuvant therapy alone. |
| format | Article |
| id | doaj-art-4657bb2b7ca24eaa9d52deee2f590b66 |
| institution | OA Journals |
| issn | 1198-0052 1718-7729 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | MDPI AG |
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| series | Current Oncology |
| spelling | doaj-art-4657bb2b7ca24eaa9d52deee2f590b662025-08-20T02:00:41ZengMDPI AGCurrent Oncology1198-00521718-77292024-12-0131127711773710.3390/curroncol31120568Braf-Mutant Melanomas: Biology and TherapyElvira Pelosi0Germana Castelli1Ugo Testa2Department of Oncology, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, ItalyDepartment of Oncology, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, ItalyDepartment of Oncology, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, ItalyThe incidence of melanoma, the most lethal form of skin cancer, has increased mainly due to ultraviolet exposure. The molecular characterization of melanomas has shown a high mutational burden led to the identification of some recurrent genetic alterations. <i>BRAF</i> gene is mutated in 40–50% of melanomas and its role in melanoma development is paramount. <i>BRAF</i> mutations confer constitutive activation of MAPK signalling. The large majority (about 90%) of <i>BRAF</i> mutations occur at amino acid 600; the majority are <i>BRAF<sup>V600E</sup></i> mutations and less frequently <i>BRAF<sup>v600K, V600D</sup></i> and <i><sup>V600M</sup></i>. The introduction of drugs that directly target <i>BRAF</i>-mutant <i>protein (BRAF inhibitors)</i> and of agents that stimulate immune response through targeting of immune check inhibitor consistently improved the survival of melanoma <i>BRAF<sup>V600</sup></i>-mutant patients with unresectable/metastatic disease. In parallel, studies in melanoma stage II-III patients with resectable disease have shown that adjuvant therapy with ICIs and/or targeted therapy improves PFS and RFS, but not OS compared to placebo; however, neoadjuvant therapy plus adjuvant therapy improved therapeutic response compared to adjuvant therapy alone.https://www.mdpi.com/1718-7729/31/12/568skin tumorsmelanomaBRAF mutationsMAPKimmunotherapytargeted therapy |
| spellingShingle | Elvira Pelosi Germana Castelli Ugo Testa Braf-Mutant Melanomas: Biology and Therapy Current Oncology skin tumors melanoma BRAF mutations MAPK immunotherapy targeted therapy |
| title | Braf-Mutant Melanomas: Biology and Therapy |
| title_full | Braf-Mutant Melanomas: Biology and Therapy |
| title_fullStr | Braf-Mutant Melanomas: Biology and Therapy |
| title_full_unstemmed | Braf-Mutant Melanomas: Biology and Therapy |
| title_short | Braf-Mutant Melanomas: Biology and Therapy |
| title_sort | braf mutant melanomas biology and therapy |
| topic | skin tumors melanoma BRAF mutations MAPK immunotherapy targeted therapy |
| url | https://www.mdpi.com/1718-7729/31/12/568 |
| work_keys_str_mv | AT elvirapelosi brafmutantmelanomasbiologyandtherapy AT germanacastelli brafmutantmelanomasbiologyandtherapy AT ugotesta brafmutantmelanomasbiologyandtherapy |