AI Article Synopsis
- Developing targeted therapies for non-p.Val600-mutant melanomas is difficult, especially in triple wildtype (TWT) cases which represent 10% of melanomas and have diverse genetic drivers.
- A patient with TWT melanoma exhibited a specific mutation, and although initially responsive to the MEK inhibitor trametinib, he eventually experienced disease progression.
- The combination of trametinib with a CDK4/6 inhibitor, palbociclib, did not improve outcomes, highlighting the complexities of treatment resistance in this type of melanoma.
Article Abstract
The development of targeted therapies for non- p.Val600-mutant melanomas remains a challenge. Triple wildtype (TWT) melanomas that lack mutations in , , or form 10% of human melanomas and are heterogeneous in their genomic drivers. mutations are enriched in -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 mutation without any 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 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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10003177 | PMC |
| http://dx.doi.org/10.3390/ijms24054520 | DOI Listing |
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