REVIEW ARTICLE Corresponding Author: M. Garshasbi Department of Medical Genetics, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran Tel: +98 21 82884569, Fax: +98 21 82884555, E-mail address: masoud.garshasbi@modares.ac.ir Pharmacogenetics and Personalized Medicine in Pancreatic Cancer Ali Hosseini Bereshneh 1 , Fatemeh Morshedi 2 , Mahsa Hematyar 3 , Arastoo Kaki 1 , and Masoud Garshasbi 1 1 Department of Medical Genetics, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran 2 Department of Genetics, School of Sciences, Science and Research Branch, Islamic Azad University, Tehran, Iran 3 Department of Biology, School of Biological Sciences, Kharazmi University, Tehran, Iran Received: 25 Dec. 2016; Revised: 08 Jan. 2017, Accepted: 12 Feb. 2017 Abstract- Pancreatic cancer ( CP ) is a progressive, fatal disease with a high degree of malignancy. More than 40000 people die from this cancer annually in the United States. As a multifactorial condition, PC has a complex nature, and there are several genes and signaling pathways implicated in PC pathogenesis and progression. There are diffèrent mutations in master genes including tumor suppressors and oncogenes that lead to Pancreatic intraepithelial neoplasia (PanIN) which is the most common non-invasive precursor lesion of pancreatic cancer. These mutations influence directly or indirectly the cycle of Pharmacodynamics profile. Interactions between genetics and drug metabolism could be considered as one of the most important insights in the personalized medicine and targeted therapy based on the genetic profile of each affected person. In this literature, we will discuss pathogenesis and susceptibility to PC, pharmacogenetics and personalized medicine in pancreatic cancer and scrutinized the most important genes, variations and signaling pathways that influence individualized therapy of PC. © 2017 Tehran University of Medical Sciences. All rights reserved. Acta Med Iran 2017;55(3):194-199. Keywords: Pancreatic cancer; Pharmacogenetics; Personalized medicine Introduction Pancreatic cancer (PC) is a progressive, fatal disease with a high degree of malignancy. Many aspects of the disease are still unknown. According to cancer statistics of United States, themortality rate of PC in men and women are about 21000 and 20000 cases respectively. Although mortality rate in both sexes is almost similar and is about 7%, but the incidence of PC in women are more than men (1). Our understanding of the genetics and molecular basis of PC has increased dramatically over the past decades and identified several germlines and somatic mutations which could be considered as master genes in the pathogenesis and progression of PC. These mutations could impact directly or indirectly on the cycle pharmacokinetic profile, and they could influence the diagnosis and therapeutic management process of the patients. New approaches such as whole exome next generation sequencing and bioinformatics analysis have yielded to vast, valuable information about the molecular biology of cancers and have discovered numbers of genes and mutations related to cancers as well as new variants which they can be important in cancer diagnosis and prognosis (2). Recently, Whole Genome Sequencing has detected an average of 63 mutations in both males and females affected. This finding demonstrates PC as a heterogeneous disease (3). The time and frequency of acquired somatic mutations specifies the duration of the normal tissue conversion into a pancreatic carcinoma tissue. This has been determined through the study of pancreatic epithelial neoplasia and PC non-progressive precursor Lesion (PanlN) (4). PanlN is graded into forms 1 to 3, and these various forms are cytologically and pathologically different. A genetic alteration in PanIN-3 is higher than other types. This higher molecular change in PanIN-3 has shown more susceptibility to progression toward malignancy. Generally, most of the patients have mutations in at least one of the following four known genes (KRAS, CDKN2A, DPC4, P53) (5). KRAS activating mutations are one of the first genetic events in PC which is mutated in 35% of PanIN- 1 and 75% of PanIN-3 lesions (6). Decreasing expression of P16/INK4A, a Tumor Suppressor Gene (T.S.G), similar to upregulation of KRAS, have been shown to influence on the transformation of PC to PanlNat early stages and includes around 85-95% of sporadic pancreas cancers. The main reason for this