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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| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-12-01
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| Series: | Current Oncology |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1718-7729/31/12/568 |
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| Summary: | 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. |
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| ISSN: | 1198-0052 1718-7729 |