التفاصيل البيبلوغرافية
| العنوان: |
Response and Resistance to Trametinib in MAP2K1-Mutant Triple-Negative Melanoma. |
| المؤلفون: |
Krebs, Fanny Seraphine, Moura, Bianca, Missiaglia, Edoardo, Aedo-Lopez, Veronica, Michielin, Olivier, Tsantoulis, Petros, Bisig, Bettina, Trimech, Mounir, Zoete, Vincent, Homicsko, Krisztian |
| المصدر: |
International Journal of Molecular Sciences; Mar2023, Vol. 24 Issue 5, p4520, 12p |
| مصطلحات موضوعية: |
CYCLIN-dependent kinase inhibitors, GENOMICS, MELANOMA, NATURAL immunity, BRAF genes |
| مستخلص: |
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. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
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