New targeted therapies in pancreatic cancer

World J Gastroenterol. 2015 May 28;21(20):6127-45. doi: 10.3748/wjg.v21.i20.6127.


Patients with pancreatic cancer have a poor prognosis with a median survival of 4-6 mo and a 5-year survival of less than 5%. Despite therapy with gemcitabine, patient survival does not exceed 6 mo, likely due to natural resistance to gemcitabine. Therefore, it is hoped that more favorable results can be obtained by using guided immunotherapy against molecular targets. This review summarizes the new leading targeted therapies in pancreatic cancers, focusing on passive and specific immunotherapies. Passive immunotherapy may have a role for treatment in combination with radiochemotherapy, which otherwise destroys the immune system along with tumor cells. It includes mainly therapies targeting against kinases, including epidermal growth factor receptor, Ras/Raf/mitogen-activated protein kinase cascade, human epidermal growth factor receptor 2, insulin growth factor-1 receptor, phosphoinositide 3-kinase/Akt/mTOR and hepatocyte growth factor receptor. Therapies against DNA repair genes, histone deacetylases, microRNA, and pancreatic tumor tissue stromal elements (stromal extracellular matric and stromal pathways) are also discussed. Specific immunotherapies, such as vaccines (whole cell recombinant, peptide, and dendritic cell vaccines), adoptive cell therapy and immunotherapy targeting tumor stem cells, have the role of activating antitumor immune responses. In the future, treatments will likely include personalized medicine, tailored for numerous molecular therapeutic targets of multiple pathogenetic pathways.

Keywords: Immunotherapy; Pancreas neoplasm; Vaccines.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use*
  • Biomarkers, Tumor / antagonists & inhibitors*
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Cancer Vaccines / therapeutic use
  • DNA Repair / drug effects
  • Humans
  • Immunotherapy / methods*
  • Molecular Targeted Therapy / methods*
  • Neoplastic Stem Cells / drug effects*
  • Neoplastic Stem Cells / enzymology
  • Neoplastic Stem Cells / immunology
  • Neoplastic Stem Cells / pathology
  • Pancreatic Neoplasms / enzymology
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / immunology
  • Pancreatic Neoplasms / pathology
  • Pancreatic Neoplasms / therapy*
  • Precision Medicine
  • Protein Kinase Inhibitors / therapeutic use
  • Signal Transduction / drug effects
  • Treatment Outcome


  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Cancer Vaccines
  • Protein Kinase Inhibitors