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24 février 2023
- doi: 10.3390/ijms24054520
- issn: 1422-0067
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info:eu-repo/semantics/altIdentifier/doi/10.3390/ijms24054520
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info:eu-repo/semantics/altIdentifier/pmid/36901951
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info:eu-repo/semantics/altIdentifier/urn/urn:nbn:ch:serval-BIB_E3A48A3138B74
info:eu-repo/semantics/openAccess , CC BY 4.0 , https://creativecommons.org/licenses/by/4.0/
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Melanocytic tumor Malignant melanomaCiter ce document
F.S. Krebs et al., « Response and Resistance to Trametinib in MAP2K1-Mutant Triple-Negative Melanoma. », Serveur académique Lausannois, ID : 10.3390/ijms24054520
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The development of targeted therapies for non-BRAF p.Val600-mutant melanomas remains a challenge. Triple wildtype (TWT) melanomas that lack mutations in BRAF, NRAS, or NF1 form 10% of human melanomas and are heterogeneous in their genomic drivers. MAP2K1 mutations are enriched in BRAF-mutant melanoma and function as an innate or adaptive resistance mechanism to BRAF inhibition. Here we report the case of a patient with TWT melanoma with a bona fide MAP2K1 mutation without any BRAF mutations. We performed a structural analysis to validate that the MEK inhibitor trametinib could block this mutation. Although the patient initially responded to trametinib, he eventually progressed. The presence of a CDKN2A deletion prompted us to combine a CDK4/6 inhibitor, palbociclib, with trametinib but without clinical benefit. Genomic analysis at progression showed multiple novel copy number alterations. Our case illustrates the challenges of combining MEK1 and CDK4/6 inhibitors in case of resistance to MEK inhibitor monotherapy.