Sequencing revealed a BRAF in-frame deletion (p.N486-P490del) and TP53 mutation (p.V157G) (Figure 5A-B). Given that cell lines harboring this mutation were sensitive to MEK inhibitors but resistant to selective BRAF inhibitors in pre-clinical models (26), she was initiated on off-label treatment with the MEK1/2 inhibitor trametinib, which is FDA-approved for use in BRAFV600E mutant melanoma (Figure 5B) (29–31). Within four weeks of initiating therapy, her serum CA19–9 had fallen from 36,000 to 8,100 U/ml, and the first restaging scan done 8 weeks after initiation of trametinib showed a partial response to therapy (Figure 5C-D).