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Association details:
| Biomarker: | NRAS Q61K |
|---|---|
| Cancer: | Melanoma |
| Drug: | Mekinist (trametinib) (MEK inhibitor) + Tafinlar (dabrafenib) (BRAF inhibitor) |
| Direction: | Resistant |
Evidence:
Source:
Title:
A phase 2 clinical trial on trametinib and low-dose dabrafenib in advanced pretreated BRAFV600/NRASQ61R/K/L wild-type melanoma (TraMel-WT): Interim efficacy and safety results.
Published date:
05/19/2021
Excerpt:
CONTRADICTING EVIDENCE: This two-stage, single-center phase 2 trial investigated T 2 mg QD in patients (pts) with advanced BRAFV600/NRASQ61R/K/L wt melanoma...LD-D (50 mg BID) was added to T (pre-amend)....The ORR in 14 evaluable pts is 42.9% (5 confirmed and 1 unconfirmed partial response), the disease control rate is 71.4%.
DOI:
10.1200/JCO.2021.39.15_suppl.9529
Trial ID:
Source:
Title:
Increased MAPK reactivation in early resistance to dabrafenib/trametinib combination therapy of BRAF-mutant metastatic melanoma
Excerpt:
An acquired resistance mechanism activating the MAPK pathway was identified in 9 of 11 Prog tumours (82%; Table 1; Fig. 1); BRAF amplifications were detected in 4 (36%), MEK1/2 mutations in 3 (27%) and oncogenic NRAS mutations in 3 (27%) Prog tumours (Figs 1 and 2).
DOI:
10.1038/ncomms6694
Source:
Title:
Combinations of BRAF, MEK, and PI3K/mTOR Inhibitors Overcome Acquired Resistance to the BRAF Inhibitor GSK2118436 Dabrafenib, Mediated by NRAS or MEK Mutations
Excerpt:
Stable knockdown of NRAS with short hairpin RNA partially restored GSK2118436 sensitivity in mutant NRAS clones, whereas expression of NRAS(Q61K) or NRAS(A146T) in the A375 parental cells decreased sensitivity to GSK2118436…Our results show that NRAS and/or MEK mutations contribute to BRAF inhibitor resistance in vitro....NRASQ61K and NRASA146T promote resistance to GSK2118436.
DOI:
10.1158/1535-7163.MCT-11-0989
