DLD and melanoma: In the present study, the functional involvement of DLD in melanoma cell resistance to vemurafenib, which has never previously been reported in published studies, is suggested by: (i) the in silico studies, which evidence a different structural accessibility of DLD to trypsin digestion between parental cell lines and drug-resistant sublines; and (ii) the finding that functional inhibition of DLD enzymatic activity induces a significant inhibition of proliferation in all of the resistant sublines under investigation, but not in the parental cell lines.