A synergy screen of epigenetic modifiers and kinase inhibitors in combination with BRAFi/MEKi revealed that the pan ERBB/HER inhibitor, neratinib, could reverse the resistance observed in <i>PTEN</i> null, <i>BRAFV600E</i> cells.<h4>Conclusions</h4>The findings indicate that <i>PTEN</i> null <i>BRAFV600E</i> melanoma exhibits increased reliance on ERBB/HER signaling when treated with clinically approved BRAFi/MEKi combinations. The gene discussed is PTEN; the disease is melanoma.