Progress in the knowledge and treatment of advanced pancreatic cancer: from benchside to bedside

Cancer Treat Rev. 2014 Oct;40(9):1039-47. doi: 10.1016/j.ctrv.2014.07.003. Epub 2014 Jul 18.

Abstract

Ever since a pivotal study in 1997 demonstrated superiority of gemcitabine over 5-FU, gemcitabine monotherapy has, until recently, comprised the standard of care in patients with advanced pancreatic cancer. However, the emerging recognition of the pancreatic cancer microenvironment, including the particularly abundant stroma, as playing a key role in disease progression and resistance to chemotherapy has marked somewhat of a paradigm shift in the way treatment of advanced pancreatic cancer is viewed, with these very same biological defenses conversely offering an Achilles heel with which to combat this aggressive disease. Recently, this approach was validated for the first time in a pivotal phase III trial in which patients received nab-paclitaxel, a stroma-targeted drug, with gemcitabine. Overall survival was significantly (p<0.001) prolonged in the combination arm, compared with gemcitabine alone, and thus these convincing results pave the way forward for future treatment regimens that employ a multipronged approach, targeting not only the primary tumor but the surrounding microenvironment as well.

Keywords: Advanced pancreatic cancer; Clinical trial; Palliative chemotherapy; Tumor microenvironment; Tumor stroma.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Albumins / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Clinical Trials as Topic
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives
  • Drug Resistance, Neoplasm
  • Epithelial-Mesenchymal Transition / drug effects
  • Fluorouracil / administration & dosage
  • Humans
  • Hyaluronic Acid / metabolism
  • Mast Cells / drug effects
  • Paclitaxel / administration & dosage
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / mortality
  • Pancreatic Neoplasms / pathology*
  • Stromal Cells / drug effects*
  • Stromal Cells / pathology
  • Treatment Outcome
  • Tumor Microenvironment / drug effects

Substances

  • 130-nm albumin-bound paclitaxel
  • Albumins
  • Deoxycytidine
  • Hyaluronic Acid
  • gemcitabine
  • Paclitaxel
  • Fluorouracil