title: Leveraging Mechanisms Governing Pancreatic Tumorigenesis To Reduce Pancreatic Cancer Mortality.
abstract: Pancreatic ductal adenocarcinoma (PDA) is a devastating malignancy with limited and modest clinical treatments. High-throughput technologies and accurate disease models now provide a comprehensive picture of the diverse molecular signaling pathways and cellular processes governing PDA tumorigenesis. Central among these is oncogenic KRAS, a mediator of cellular plasticity, metabolic reprogramming, and inflammatory and paracrine signaling required for tumor development and maintenance. Biological aggressiveness is further conferred by a highly fibrotic and immunosuppressive PDA microenvironment that also acts as a barrier to effective drug delivery. The regulation of these mechanisms and their implications for early cancer detection, chemoprevention and therapy are discussed.
authors.affiliation: Department of Surgery, David Geffen School of Medicine, University of California Los Angeles (UCLA), Los Angeles, CA 90095, USA; Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, UCLA, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, UCLA, Los Angeles, CA 90095, USA.
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Donahue
authors.affiliation: Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, UCLA, Los Angeles, CA 90095, USA; Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, UCLA, Los Angeles, CA 90095, USA. Electronic address: ddawson@mednet.ucla.edu.
authors.forename: David W
authors.initials: DW
authors.lastname: Dawson
mesh_terms: D000818:Animals; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D057285:Precision Medicine / Q000379:methods; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
chemical_list: D016283:Proto-Oncogene Proteins p21(ras)
keywords: KRAS; immunotherapy; pancreatic cancer; precision medicine; tumor–stroma interactions