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International Journal Of Bilogical Sciences

.: Home > International Journal Of Bilogical Sciences > 2016 > Volume 12 Number 3 > Saswati Chand, Kevin O'Hayer, Fernando F. Blanco, Jordan M. Winter, Jonathan R. Brody

The Landscape of Pancreatic Cancer Therapeutic Resistance Mechanisms

Saswati Chand, Kevin O'Hayer, Fernando F. Blanco, Jordan M. Winter, Jonathan R. Brody
1. Department of Surgery, The Jefferson Pancreas, Biliary, and Related Cancer Center; 2. Department of Medical Oncology, and the 3. Department of Pharmacology & Experimental Therapeutics, Division of Clinical Pharmacology, Thomas Jefferson University, Philadelphia PA.  Corresponding author: Jonathan R. Brody, Ph.D., Department of Surgery, Thomas Jefferson University. 1015 Walnut Street Ste 620, Curtis Bldg, Philadelphia, PA 19107. Email: jonathan.brody@jefferson.edu, Telephone: (215) 955-2693; Fax: (215) 923-6609
Abstract :

Pancreatic cancer (pancreatic ductal adenocarcinoma, PDA) is infamously moving to the top of the list as one of the most lethal cancers with an overall 5 year survival rate of 7%. Multiple genomic-based and molecular characterization studies of PDA specimens and established animal models have provided the field with multiple targets and a progression model of this disease. Still, to date, the best therapeutic options are surgery and combination cytotoxic therapies. In general, even in the best case scenario (i.e., an early stage diagnosis and a response to a specific therapy), most of these fortunate patients’ PDA cells acquire or exert resistance mechanisms and eventually kill the patient. Herein, we touch on a growing field of investigation that focuses on PDA cell therapeutic resistance mechanisms. We examine extrinsic elements (i.e., the tumor microenvironment, hypoxia) to the intrinsic processes within the cell (i.e., post-transcriptional gene regulation and somatic mutations) that are important for therapeutic efficacy and resistance. Even as better targeted and personalized approaches move through the clinical trial pipeline the discussed resistance mechanisms will most likely play a role in the management of this deadly disease. 

Keywords :
Pancreatic Ductal Adenocarcinoma, Chemotherapeutic Resistance, Hypoxia, HuR, DNA Damage

Date Deposited : 16 Mar 2016 10:55

Last Modified : 16 Mar 2016 10:55

Official URL: http://www.ijbs.com/v12i3

Volume 12, Number 3, - 2016 , ISSN 1449-2288

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