The EDT specimen provides a unique opportunity to investigate the early changes that occur in a melanoma tumour with MAPK inhibitors that may set up for later resistance or complete response, and that may be amenable to therapeutic manipulation. For example, EDT samples collected on patients treated with single agent BRAF inhibitors showed increased T cell infiltrate that was associated with a better response in the lesion. The T cell infiltrate has also been associated with increased expression of melanoma antigens, a decrease in immunosuppressive cytokines [interleukin (IL)-6 and IL-8] and an increase in markers of T-cell cytotoxicity. Additional studies have shown the expected suppression in pERK, and in paired PRE-EDT samples, the decreased ERK suppression is associated with a better RECIST response. There have been no reports of the effects of BRAF and MEK inhibitors as single agent or in combination on responding melanoma tissue taken more than 15 days after commencement of treatment. As the median PFS for the combination of dabrafenib and trametinib is 9.4 months, >95% of the POST samples will be responding, and provide an opportunity to 1) compare the responding POST with the EDT sample (and the baseline PRE samples prior to treatment) to investigate how signalling pathways (as determined by RNA gene expression and protein expression) alter with time, and 2) how the changes in signalling pathways correlate with clinical and pathological response.