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Association details:
| Biomarker: | NRAS Q61R |
|---|---|
| Cancer: | Melanoma |
| Drug: | Zelboraf (vemurafenib) (BRAF inhibitor, BRAF V600E inhibitor) |
| Direction: | Resistant |
Evidence:
Source:
Title:
Identification of Multiple Mechanisms of Resistance to Vemurafenib in a Patient with BRAFV600E-Mutated Cutaneous Melanoma Successfully Rechallenged after Progression
Excerpt:
We identified two NRAS-activating somatic mutations, Q61R and Q61K, affecting two main subpopulations in the metastasis PV1 and a BRAF alternative splicing, involving exons 4-10, in the metastasis PV2. These alterations, known to confer resistance to RAF inhibitors, were tumor-specific, mutually exclusive, and were not detected in pretreatment tumor samples.
DOI:
10.1158/1078-0432.CCR-13-0661
Source:
Title:
Melanomas acquire resistance to B-RAF(V600E) inhibition by RTK or N-RAS upregulation
Excerpt:
In M249 R4, we sequenced all exons of N-RAS, K-RAS (also known as KRAS) or H-RAS (also known as HRAS)...This patient continued on therapy with PLX4032 until 6 months later, when several other nodal metastases developed (Supplementary Fig. 14a, b). Analysis of a biopsy taken at a second progression site (Pt55 DP2) demonstrated a different mutation in N-RAS, N-RAS(Q61R) (Supplementary Fig. 14b).
DOI:
10.1038/nature09626
