title: Neural Regulation of Pancreatic Cancer: A Novel Target for Intervention.
abstract: The tumor microenvironment is known to play a pivotal role in driving cancer progression and governing response to therapy. This is of significance in pancreatic cancer where the unique pancreatic tumor microenvironment, characterized by its pronounced desmoplasia and fibrosis, drives early stages of tumor progression and dissemination, and contributes to its associated low survival rates. Several molecular factors that regulate interactions between pancreatic tumors and their surrounding stroma are beginning to be identified. Yet broader physiological factors that influence these interactions remain unclear. Here, we discuss a series of preclinical and mechanistic studies that highlight the important role chronic stress plays as a physiological regulator of neural-tumor interactions in driving the progression of pancreatic cancer. These studies propose several approaches to target stress signaling via the β-adrenergic signaling pathway in order to slow pancreatic tumor growth and metastasis. They also provide evidence to support the use of β-blockers as a novel therapeutic intervention to complement current clinical strategies to improve cancer outcome in patients with pancreatic cancer.
authors.affiliation: Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia. aeson.chang@monash.edu.
authors.forename: Aeson
authors.initials: A
authors.lastname: Chang
authors.affiliation: Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia. corina.kim-fuchs@insel.ch.|Department of Visceral Surgery and Medicine, University Hospital Bern, Bern 3010, Switzerland. corina.kim-fuchs@insel.ch.
authors.forename: Corina
authors.initials: C
authors.lastname: Kim-Fuchs
authors.affiliation: Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia. caroline.le@monash.edu.
authors.forename: Caroline P
authors.initials: CP
authors.lastname: Le
authors.affiliation: Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia. frederic.hollande@unimelb.edu.au.|Department of Pathology, University of Melbourne, Parkville 3010, Australia. frederic.hollande@unimelb.edu.au.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Hollande
authors.affiliation: Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia. erica.sloan@monash.edu.|Cousins Center for PNI, UCLA Semel Institute, Jonsson Comprehensive Cancer Center, and UCLA AIDS Institute, University of California Los Angeles, Los Angeles, CA 90095, USA. erica.sloan@monash.edu.|Peter MacCallum Cancer Centre, Division of Cancer Surgery, East Melbourne, Victoria 3002, Australia. erica.sloan@monash.edu.
authors.forename: Erica K
authors.initials: EK
authors.lastname: Sloan
keywords: beta-adrenergic; beta-blockers; metastasis; neural; pancreatic cancer; stress