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Association details:
| Biomarker: | MAP2K1 C121S |
|---|---|
| Cancer: | Melanoma |
| Drug: | Zelboraf (vemurafenib) (BRAF inhibitor, BRAF V600E inhibitor) |
| Direction: | Resistant |
Evidence:
Source:
Title:
Dissecting therapeutic resistance to RAF inhibition in melanoma by tumor genomic profiling
Excerpt:
...a patient with melanoma who developed resistance to PLX4032 after an initial dramatic response. The resulting profile identified an activating mutation at codon 121 in the downstream kinase MEK1…Thus, MEK1(C121S) or functionally similar mutations are predicted to confer resistance to combined MEK/RAF inhibition.
DOI:
10.1200/JCO.2010.33.2312
Source:
Title:
Novel ATP-competitive MEK inhibitor E6201 is effective against vemurafenib-resistant melanoma harboring the MEK1-C121S mutation in a preclinical model
Excerpt:
We found that the acquired MEK1-C121S mutation in BRAF-V600E mutant melanoma conferred resistance to both vemurafenib and selumetinib but not E6201. The effectiveness of E6201 in this preclinical study is a result of its binding with MEK1 far from the C121S point mutation so the mutation is unable to influence the MAPK pathway inhibitory activity. These results support further clinical investigation of E6201.
DOI:
10.1158/1535-7163.MCT-13-0667
