Advanced pancreatic cancer: flourishing novel approaches in the era of biological therapy

Oncologist. 2014 Sep;19(9):937-50. doi: 10.1634/theoncologist.2012-0131. Epub 2014 Aug 12.

Abstract

The progress in the development of systemic treatment for advanced pancreatic cancer (APC) has been slow. The mainstream treatment remains using chemotherapy including gemcitabine, FOLFIRINOX, and nab-paclitaxel. Erlotinib is the only approved biological therapy with marginal benefit. Studies of agents targeting epidermal growth factor receptor, angiogenesis, and RAS signaling have not been satisfying, and the usefulness of targeted therapy in APC is uncertain. Understanding in molecular processes and tumor biology has opened the door for new treatment strategies such as targeting insulin-like growth factor 1 receptor, transforming growth factor β, phosphoinositide 3-kinase/AKT/mammalian target of rapamycin pathway, and Notch pathway. New directions also include the upcoming immunotherapy and many novel agents that act on the microenvironment. The practice of personalized medicine using predictive biomarkers and pharmacogenomics signatures may also enhance the effectiveness of existing treatment. Future treatment approaches may involve comprehensive genomic assessment of tumor and integrated combinations of multiple agents to overcome treatment resistance.

Keywords: Advanced pancreatic cancer; Biological therapy; Gemcitabine; Targeted therapy.

MeSH terms

  • Biomarkers, Tumor
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine / therapeutic use
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism
  • Erlotinib Hydrochloride
  • Gemcitabine
  • Humans
  • Molecular Targeted Therapy*
  • Neoplasm Staging
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / pathology
  • Precision Medicine
  • Protein Kinase Inhibitors / therapeutic use*
  • Quinazolines / therapeutic use
  • Signal Transduction / drug effects
  • Signal Transduction / genetics

Substances

  • Biomarkers, Tumor
  • Protein Kinase Inhibitors
  • Quinazolines
  • Deoxycytidine
  • Erlotinib Hydrochloride
  • ErbB Receptors
  • Gemcitabine