title: Targeting reactive oxygen species in development and progression of pancreatic cancer.
abstract: Pancreatic ductal adenocarcinoma (PDA) is characterized by expression of oncogenic KRas which drives all aspects of tumorigenesis. Oncogenic KRas induces the formation of reactive oxygen species (ROS) which have been implicated in initiation and progression of PDA. To facilitate tumor promoting levels and to avoid oncogene-induced senescence or cytotoxicity, ROS homeostasis in PDA cells is balanced by additional up-regulation of antioxidant systems. Areas covered: We examine the sources of ROS in PDA, the mechanisms by which ROS homeostasis is maintained, and the biological consequences of ROS in PDA. Additionally, we discuss the potential mechanisms for targeting ROS homoeostasis as a point of therapeutic intervention. An extensive review of the relevant literature as it relates to the topic was conducted using PubMed. Expert commentary: Even though oncogenic mutations in the KRAS gene have been detected in over 95% of human pancreatic adenocarcinoma, targeting its gene product, KRas, has been difficult. The dependency of PDA cells on balancing ROS homeostasis could be an angle for new prevention or treatment strategies. These include use of antioxidants to prevent formation or progression of precancerous lesions, or methods to increase ROS in tumor cells to toxic levels.
authors.affiliation: a Department of Cancer Biology , Mayo Clinic , Jacksonville , FL , USA.
authors.forename: Nisha
authors.initials: N
authors.lastname: Durand
authors.affiliation: a Department of Cancer Biology , Mayo Clinic , Jacksonville , FL , USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Storz
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology*; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000378:metabolism; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics / Q000473:pathology*; D018450:Disease Progression; D006801:Humans; D009154:Mutation; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000473:pathology*; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000975:Antioxidants; C117307:KRAS protein, human; D017382:Reactive Oxygen Species; D016283:Proto-Oncogene Proteins p21(ras)
keywords: KRas; NOX; PanIN; Reactive oxygen species; antioxidants; mitochondria; pancreatic cancer