Novel targets in pancreatic cancer research.
The initiation and progression of pancreatic ductal adenocarcinoma (PDA) occurs as a result of molecular alterations that typically result in fluctuations of transcription, protein expression, and ultimately dysregulated signaling pathways. For example, PDA is driven by key activating, gain-of-function mutations in proto-oncogenes (eg, K-Ras) along with loss of function of tumor suppressor genes (eg, p16, SMAD4). With the advent of whole-exome sequencing of PDA genomes, several key genetic alterations have been identified as drivers of PDA. While these findings have led to groundbreaking discoveries in the etiology of PDA, they have failed to provide feasible, targetable therapeutic approaches. Additionally, recent advances in PDA research have uncovered the role of the tumor microenvironment (the non-epithelial tumor cells) in PDA progression by promoting potent, acute changes in gene expression. Herein, this chapter is aimed at discussing the key genetic and non-genetic mechanisms responsible for PDA initiation and progression. Thus based on these mechanisms, we will put forth investigated and novel therapeutic targets in PDA.
Department of Surgery, Jefferson Center for Pancreatic, Biliary and Related Cancers, Thomas Jefferson University, Philadelphia, PA.
Geoffrey
G
Kozak
Department of Surgery, Jefferson Center for Pancreatic, Biliary and Related Cancers, Thomas Jefferson University, Philadelphia, PA; Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, PA.
Fernando F
FF
Blanco
Department of Surgery, Jefferson Center for Pancreatic, Biliary and Related Cancers, Thomas Jefferson University, Philadelphia, PA. Electronic address: jonathan.brody@jefferson.edu.
Jonathan R
JR
Brody
D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D021441:Carcinoma, Pancreatic Ductal / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006801:Humans; D056747:Immunomodulation; D058990:Molecular Targeted Therapy; D009154:Mutation; D009857:Oncogenes; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000378:metabolism
D014408:Biomarkers, Tumor