Attenuating PI3K isoforms in pancreatic cancer: Focus on immune PI3Kγ

Clin Res Hepatol Gastroenterol. 2017 Sep;41(4):351-353. doi: 10.1016/j.clinre.2017.04.013. Epub 2017 Jun 2.

Abstract

Phosphoinositide 3-kinases PI3Ks are major drug targets in oncology. Their role is far from being completely understood in pancreatic ductal adenocarcinoma. Pancreatic cancer is a dismal disease with limited therapeutic options except for surgery. We highlight here two elegant works demonstrating the role of PI3Kγ in cancer-associated macrophages applied in particular to pancreatic tumors. These data open new avenues for the use of PI3K-targetting drugs in cancer as anti-stroma therapies. Amongst the classI PI3K isoforms, PI3Kγ and PI3Kδ, are highly expressed in immune cells. Isoform-specific or pan-class I PI3K inhibitors which target all classI PI3Ks could be used as a targeted therapy towards cancer cell signaling but also as immunotherapies. Research on immunoregulation of human pancreatic cancer by the other ubiquitous α- or β-isoforms of PI3K needs to be performed.

Keywords: Anti-stroma therapy; PI3K; Pancreatic ductal adenocarcinoma.

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / immunology*
  • Animals
  • Class Ib Phosphatidylinositol 3-Kinase / immunology*
  • Humans
  • Macrophages / immunology*
  • Mice
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / immunology*
  • Phosphoinositide-3 Kinase Inhibitors*
  • Protein Isoforms / antagonists & inhibitors

Substances

  • Phosphoinositide-3 Kinase Inhibitors
  • Protein Isoforms
  • Class Ib Phosphatidylinositol 3-Kinase
  • PIK3CG protein, human