Oncogenic BRAF and NRAS mutations are frequent in malignant melanoma. BRAF that 
is activated by the common V600E and other mutations, as well as by upstream 
NRAS mutations, has been shown to require the molecular chaperone heat shock 
protein 90 (HSP90) for stabilization and is depleted by the HSP90 inhibitor 
17-allylamino-17-demethoxygeldanamycin (17-AAG)]. Here, we explore the possible 
relationship between tumor BRAF and NRAS mutations and clinical response to 
17-AAG in six patients with metastatic malignant melanoma who received 
pharmacologically active doses of 17-AAG as part of a phase I clinical trial. 
One patient with disease stabilization for 49 months had a (G13D)NRAS mutation 
and (WT)BRAF. A second patient who had stable disease for 15 months had a 
(V600E)BRAF mutation and (WT)NRAS. These preliminary results suggest that BRAF 
and NRAS mutation status should be determined in prospective phase II studies of 
HSP90 inhibitors in melanoma.