Epidemiological-molecular evidence of metabolic reprogramming on proliferation, autophagy and cell signaling in pancreas cancer.
Pancreatic cancer remains one of the deadliest human cancers with little progress made in survival over the past decades, and 5-year survival usually below 5%. Despite this dismal scenario, progresses have been made in understanding of the underlying tumor biology through among other definition of precursor lesions, delineation of molecular pathways, and advances in genome-wide technology. Further, exploring the relationship between epidemiological risk factors involving metabolic features to that of an altered cancer metabolism may provide the foundation for new therapies. Here we explore how nutrients and caloric intake may influence the KRAS-driven ductal carcinogenesis through mediators of metabolic stress, including autophagy in presence of TP53, advanced glycation end products (AGE) and the receptors (RAGE) and ligands (HMGB1), as well as glutamine pathways, among others. Effective understanding the cancer metabolism mechanisms in pancreatic cancer may propose new ways of prevention and treatment.
Department of Gastrointestinal Surgery, Stavanger University Hospital, Stavanger, Norway; Department of Clinical Medicine, University of Bergen, Bergen, Norway. Electronic address: ksoreide@mac.com.
Kjetil
K
Søreide
Department of Surgical and Perioperative Sciences, Surgery, Umeå University, Umeå, Sweden.
Malin
M
Sund
D000818:Animals; D001343:Autophagy / Q000235:genetics*; D021441:Carcinoma, Pancreatic Ductal / Q000453:epidemiology / Q000235:genetics / Q000473:pathology*; D049109:Cell Proliferation; D065150:Cellular Reprogramming / Q000235:genetics*; D048909:Diabetes Complications / Q000378:metabolism; D002149:Energy Intake; D015972:Gene Expression Regulation, Neoplastic; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006019:Glycolysis; D024243:HMGB1 Protein / Q000378:metabolism; D006801:Humans; D051379:Mice; D009765:Obesity / Q000150:complications; D010190:Pancreatic Neoplasms / Q000453:epidemiology* / Q000378:metabolism* / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras); D000067759:Receptor for Advanced Glycation End Products / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis; D018631:ras Proteins / Q000378:metabolism
D017127:Glycation End Products, Advanced; D024243:HMGB1 Protein; C585491:HMGB1 protein, human; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D000067759:Receptor for Advanced Glycation End Products; D016159:Tumor Suppressor Protein p53; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins
Autophagy; Cancer metabolism; Glycolysis; KRAS mutation; Pancreas cancer