title: Molecular Drivers of Pancreatic Cancer Pathogenesis: Looking Inward to Move Forward.
abstract: Pancreatic cancer (PC) continues to rank among the most lethal cancers. The consistent increase in incidence and mortality has made it the seventh leading cause of cancer-associated deaths globally and the third in the United States. The biggest challenge in combating PC is our insufficient understanding of the molecular mechanism(s) underlying its complex biology. Studies during the last several years have helped identify several putative factors and events, both genetic and epigenetic, as well as some deregulated signaling pathways, with implications in PC onset and progression. In this review article, we make an effort to summarize our current understanding of molecular and cellular events involved in the pathogenesis of pancreatic malignancy. Specifically, we provide up-to-date information on the genetic and epigenetic changes that occur during the initiation and progression of PC and their functional involvement in the pathogenic processes. We also discuss the impact of the tumor microenvironment on the molecular landscape of PC and its role in aggressive disease progression. It is envisioned that a better understanding of these molecular factors and the mechanisms of their actions can help unravel novel diagnostic and prognostic biomarkers and can also be exploited for future targeted therapies.
authors.affiliation: Department of Oncologic Sciences, Mitchell Cancer Institute, University of South Alabama, Mobile, AL 36604, USA. makhan@health.southalabama.edu.
authors.forename: Mohammad Aslam Aslam
authors.initials: MA
authors.lastname: Khan
authors.affiliation: Department of Oncologic Sciences, Mitchell Cancer Institute, University of South Alabama, Mobile, AL 36604, USA. sazim@health.southalabama.edu.
authors.forename: Shafquat
authors.initials: S
authors.lastname: Azim
authors.affiliation: Department of Oncologic Sciences, Mitchell Cancer Institute, University of South Alabama, Mobile, AL 36604, USA. hzubair@health.southalabama.edu.
authors.forename: Haseeb
authors.initials: H
authors.lastname: Zubair
authors.affiliation: Department of Oncologic Sciences, Mitchell Cancer Institute, University of South Alabama, Mobile, AL 36604, USA. abhardwaj@health.southalabama.edu.
authors.forename: Arun
authors.initials: A
authors.lastname: Bhardwaj
authors.affiliation: Department of Oncologic Sciences, Mitchell Cancer Institute, University of South Alabama, Mobile, AL 36604, USA. gpatel@health.southalabama.edu.
authors.forename: Girijesh Kumar
authors.initials: GK
authors.lastname: Patel
authors.affiliation: Departments of Interdisciplinary Clinical Oncology, Mitchell Cancer Institute, University of South Alabama, Mobile, AL 36604, USA. mmkhushman@health.southalabama.edu.
authors.forename: Moh'd
authors.initials: M
authors.lastname: Khushman
authors.affiliation: Department of Oncologic Sciences, Mitchell Cancer Institute, University of South Alabama, Mobile, AL 36604, USA. seemasingh@health.southalabama.edu.|Department of Biochemistry and Molecular Biology, College of Medicine, University of South Alabama, Mobile, AL 36604, USA. seemasingh@health.southalabama.edu.
authors.forename: Seema
authors.initials: S
authors.lastname: Singh
authors.affiliation: Department of Oncologic Sciences, Mitchell Cancer Institute, University of South Alabama, Mobile, AL 36604, USA. asingh@health.southalabama.edu.|Department of Biochemistry and Molecular Biology, College of Medicine, University of South Alabama, Mobile, AL 36604, USA. asingh@health.southalabama.edu.
authors.forename: Ajay Pratap
authors.initials: AP
authors.lastname: Singh
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D018450:Disease Progression; D044127:Epigenesis, Genetic; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D006801:Humans; D058990:Molecular Targeted Therapy; D009154:Mutation; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000473:pathology*; D059016:Tumor Microenvironment
chemical_list: D014408:Biomarkers, Tumor
keywords: microRNA; molecular pathogenesis; mutations; non-coding RNAs; pancreatic ductal adenocarcinoma; tumor microenvironment