Oncogene amplification mediates resistance to melanoma drugs

Some melanoma patients resistant to the B-RAF inhibitor drug vemurafenib harbour amplifications in B-RAF reports a study published in Nature Communications this week. The work sheds light on the mechanisms of tumour resistance for these melanoma patients and suggests an alternative way of treating resistant melanomas. The kinase B-RAF is mutated in a large proportion of melanomas and B-RAF inhibitors, for instance vemurafenib, have been developed to treat melanoma. Unfortunately, a proportion of patients develop resistance to the drug and relapse. By sequencing the genes of 20 patients before and after developing vemurafenib resistance, Roger Lo and colleagues found that 6 of the patients showed increased copy number of the mutant B-RAF gene. Cell lines derived from these patients also showed an increase in the activation of the downstream kinase ERK. The authors demonstrate that treatment of the cancercells in culture with both vermurafenib and small molecules that block ERK activation, worked together to reduce cell growth. These findings suggest that this dual inhibition may be a useful way of treating resistant melanomas.