title: Challenges and future directions in therapeutics for pancreatic ductal adenocarcinoma.
abstract: BACKGROUND
  Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer death in the USA. The 5-year survival of < 5% has not changed in decades. In contrast to other major cancers, the incidence of PDAC is increasing.
  
  
  METHODS
  The aims of this paper are first to analyze why PDAC is so difficult to treat and, second, to suggest future directions for PDAC therapeutics. The authors provide an article that is based on a comprehensive search through MEDLINE and the clinicalTrials.gov website.
  
  
  CONCLUSIONS
  Progress has been made recently. Notably, FOLFIRINOX or nab-paclitaxel plus gemcitabine provide survival benefit over gemcitabine alone, which was previously the mainstay of therapy for PDAC. Most of the current trials are testing combinations of repurposed drugs rather than addressing key targets in the PDAC pathogenesis. It is clear that to really make an impact on this disease, it will be necessary to address three different problems with targeted therapeutics. First, it is important to eradicate PDAC stem cells that result in recurrence. Second, it is important to reduce the peritumoral stroma that provides the tumors with growth support and provides a barrier to access of therapeutic agents. Finally, it is important to address the marked cachexia and metabolic derangement that contribute to morbidity and mortality and further complicate therapeutic intervention.
authors: Department of Physiology, College of Medicine and Health Sciences, United Arab Emirates University , PO Box 17666, Al Ain , UAE.
authors: Amal H I
authors: AH
authors: Al Haddad
authors: Thomas E
authors: TE
authors: Adrian
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002100:Cachexia / Q000209:etiology / Q000628:therapy; D021441:Carcinoma, Pancreatic Ductal / Q000188:drug therapy* / Q000453:epidemiology / Q000473:pathology; D002986:Clinical Trials as Topic; D015195:Drug Design; D006801:Humans; D015994:Incidence; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control; D014411:Neoplastic Stem Cells / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000453:epidemiology / Q000473:pathology; D015996:Survival Rate
keywords: cachexia; cancer stem cells; pancreatic cancer; pancreatic ductal adenocarcinoma; therapy; tumor microenvironment