KRAS and neoplasm: However, our patient had multiple alterations that could activate the MEK pathway (GNAS R201C, KRAS G12D, and NF1 D1976fs) [29–33] and demonstrated a remarkable responsiveness to the MEK inhibitor trametinib, with a steep decline in CA19-9 and %ctDNA as well as improvement in symptoms and PET imaging after therapy showing only minimal uptake in the tumor (Fig. 3).