Moreover, in our work, combined inhibition of MEK1/2 (with trametinib) plus inhibition of lysosome function (with CQ or HCQ) displayed synergistic antiproliferative activity in vitro, superior tumor control (compared to the single agents or standard of care) in cell line- or patient-derived xenografts (CDX or PDX) models of pancreatic cancer and, in one patient with advanced pancreatic cancer, there was evidence of antitumor activity of the combination of trametinib plus HCQ (Kinsey et al., 2019). Here, MAP2K1 is linked to familial pancreatic carcinoma.