We have updated the scientific knowledge in this area by demonstrating that the inactivation of PCSK6 could suppress the Raf-MEK1/2-ERK1/2 signaling pathway to restrain tumor progression and liver metastasis, thus providing a promising and attractive target for tailored therapies to overcome challenges from mutated KRAS, however, in-depth evaluations of this novel target and therapeutic strategy in pancreatic cancer remain essential. The gene discussed is MAP2K1; the disease is familial pancreatic carcinoma.