Translational Therapeutic Opportunities in Ductal Adenocarcinoma of the Pancreas

• Published in: Clinical cancer research Vol. 18; no. 16; pp. 4249 - 4256
• Main Authors: HIDALGO, Manuel, VON HOFF, Daniel D
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15.08.2012
• Subjects: Animals; Antineoplastic agents; Biological and medical sciences; Biomarkers, Tumor - genetics; Carcinoma, Pancreatic Ductal - genetics; Carcinoma, Pancreatic Ductal - metabolism; Carcinoma, Pancreatic Ductal - therapy; Humans; Medical sciences; Molecular Targeted Therapy; Neoplastic Stem Cells - metabolism; Pancreatic Neoplasms - genetics; Pancreatic Neoplasms - metabolism; Pancreatic Neoplasms - therapy; Pharmacology. Drug treatments; Tumor Microenvironment - genetics; Adenocarcinoma; Treatment; Malignant tumor; Pancreas; Genetic translation; Cancer
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.ccr-12-1327

Pancreatic ductal adenocarcinoma (PDA) remains a devastating disease with nearly equal incidence and mortality rates. Over the past few decades, a litany of randomized clinical trials has failed to improve the outcome of this disease. More recently, the combination chemotherapy regimen FOLFIRINOX has shown improvement in overall survival over the single agent gemcitabine, and nab-paclitaxel (an albumin-coated formulation of paclitaxel) in combination with gemcitabine has shown promising results in phase II studies. Despite limited impact on patient care as of yet, the molecular and biologic understanding of PDA has advanced substantially. This includes understanding the genomic complexity of the disease, the potential importance of the tumor microenvironment, the metabolic adaptation of PDA cells to obtain nutrients in a hypoxic environment, and the role of pancreatic cancer stem cells. These fundamental discoveries are starting to be translated into clinical studies. In this overview, we discuss the implications of biologic understanding of PDA in clinical research and provide insights for future development of novel approaches and agents in this disease.