Pancreatic cancer has one of the highest rates of mortality among malignancies and the development of promising future therapies is strongly required. Recently, the utility of gene aberrations as biomarkers for determining therapeutic strategies has been demonstrated in several types of cancer. The detection of druggable mutations that aid in the selection of effective molecular targeting drugs is feasible in clinical settings for certain cancers. On the other hand, personalized therapy for pancreatic cancer guided by genomic biomarkers has not yet been realized and suitable molecular targets for the disease have been unclear until now. KRAS, CDKN2A, TP53, and SMAD4 have been recognized as major driver genes in pancreatic carcinogenesis. However, it is considered difficult to develop treatment strategies to target genetic aberrations of these four genes. In recent years, genome sequencing has progressively revealed the molecular biological characteristics of pancreatic cancer, including the discovery of novel potential therapeutic targets and low-frequency druggable genetic aberrations. Gene profilebased novel treatment strategies and subsequent attempts to realize precision medicine for pancreatic cancer are steadily ongoing in an effort to achieve improved treatment outcomes.