- Open Access
Incidence of the V600K mutation among melanoma patients with BRAF mutations, and potential therapeutic response to the specific BRAF inhibitor PLX4032
© Rubinstein et al; licensee BioMed Central Ltd. 2010
- Received: 12 May 2010
- Accepted: 14 July 2010
- Published: 14 July 2010
Activating mutations in BRAF kinase are common in melanomas. Clinical trials with PLX4032, the mutant-BRAF inhibitor, show promising preliminary results in patients selected for the presence of V600E mutation. However, activating V600K mutation is the other most common mutation, yet patients with this variant are currently excluded from the PLX4032 trials. Here we present evidence that a patient bearing the BRAF V600K mutation responded remarkably to PLX4032, suggesting that clinical trials should include all patients with activating BRAF V600E/K mutations.
- Melanoma Patient
- BRAF Mutation
- BRAF V600E Mutation
Our data, and those of others reported in the literature, indicate that the incidence of BRAF V600K mutations in melanoma patients appears to be higher than is commonly assumed. It can be present in up to 30% of patients bearing BRAF V600 mutations, potentially representing up to 10% of all melanoma patients. Patients with BRAF V600K mutations are currently excluded from clinical trials with PLX4032, although the assay methodology used for the trial may not discriminate between the V600E and V600K mutations. Our preclinical data demonstrating similar kinase activity of the V600K and V600E mutations, together with clear evidence of clinical activity of PLX4032 in a patient with a documented V600K mutation, suggest that melanoma patients with V600K mutations should be included in current and future trials of BRAF inhibitors.
This work was supported by the Yale SPORE in Skin Cancer funded by the National Cancer Institute grant number 1 P50 CA121974 (R. Halaban, PI). Written consent for publication was obtained from the patient.
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