title: Pancreatic cancer: Stroma and its current and emerging targeted therapies.
abstract: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal human malignancies with a 5-year survival rate of 8%. Dense, fibrotic stroma associated with pancreatic tumors is a major obstacle for drug delivery to the tumor bed and plays a crucial role in pancreatic cancer progression. Targeting stroma is considered as a potential therapeutic strategy to improve anti-cancer drug efficacy and patient survival. Although numerous stromal depletion therapies have reached the clinic, they add little to overall survival and are often associated with toxicity. Furthermore, increasing evidence suggests the anti-tumor properties of stroma. Its complete ablation enhanced tumor progression and reduced survival. Consequently, efforts are now focused on developing stromal-targeted therapies that normalize the reactive stroma and avoid the extremes: stromal abundance vs. complete depletion. In this review, we summarized the state of current and emerging anti-stromal targeted therapies, with major emphasis on the role of miRNAs in PDAC stroma and their potential use as novel therapeutic agents to modulate PDAC tumor-stromal interactions.
authors.affiliation: Department of Medical and Molecular Genetics, Indiana University School of Medicine (IUSM), Indianapolis, IN, USA; The Melvin and Bren Simon Cancer Center, IUSM, Indianapolis, IN, USA; Center for Pancreatic Cancer Research, Indiana University and Purdue University-Indianapolis (IUPUI), Indianapolis, IN, USA. Electronic address: jkota@iu.edu.
authors.forename: Janaiah
authors.initials: J
authors.lastname: Kota
authors.affiliation: Department of Medical and Molecular Genetics, Indiana University School of Medicine (IUSM), Indianapolis, IN, USA.
authors.forename: Julie
authors.initials: J
authors.lastname: Hancock
authors.affiliation: Department of Medical and Molecular Genetics, Indiana University School of Medicine (IUSM), Indianapolis, IN, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Kwon
authors.affiliation: The Melvin and Bren Simon Cancer Center, IUSM, Indianapolis, IN, USA; Center for Pancreatic Cancer Research, Indiana University and Purdue University-Indianapolis (IUPUI), Indianapolis, IN, USA; Department of Biochemistry and Molecular Biology, IUSM, Indianapolis, IN, USA; Department of Medicine, IUSM, Indianapolis, IN, USA.
authors.forename: Murray
authors.initials: M
authors.lastname: Korc
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology / Q000628:therapy*; D021441:Carcinoma, Pancreatic Ductal / Q000473:pathology / Q000628:therapy*; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D017154:Stromal Cells / Q000473:pathology*; D059016:Tumor Microenvironment
chemical_list: D035683:MicroRNAs
keywords: Pancreatic Cancer; Stroma; Targeted therapies; Tumor microenvironment; miRNAS