Inhibition of PI3K and MEK: it is all about combinations and biomarkers

Clin Cancer Res. 2009 Jul 15;15(14):4518-20. doi: 10.1158/1078-0432.CCR-09-0872. Epub 2009 Jul 7.

Abstract

A small molecule inhibitor of MAP/ERK kinase (MEK) was effective against human breast cancer cells with a basal-like gene expression signature. Antitumor activity was limited by both feedback upregulation of phosphatidylinositol-3 kinase (PI3K)/AKT upon inhibition of MEK as well as loss of the phosphatase PTEN. Therefore, MEK inhibitors should preferably be investigated in combination with PI3K inhibitors in basal-like breast cancers.

Publication types

  • Comment

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Biomarkers, Tumor / antagonists & inhibitors
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Enzyme Inhibitors / pharmacology*
  • Female
  • Humans
  • MAP Kinase Kinase 1 / antagonists & inhibitors*
  • MAP Kinase Kinase 1 / genetics
  • MAP Kinase Kinase 1 / metabolism
  • Mammary Neoplasms, Experimental / drug therapy
  • Mammary Neoplasms, Experimental / metabolism
  • Mammary Neoplasms, Experimental / pathology
  • Mice
  • Mice, Inbred Strains
  • Mice, Nude
  • Models, Biological
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphoinositide-3 Kinase Inhibitors*
  • Xenograft Model Antitumor Assays*

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Enzyme Inhibitors
  • Phosphoinositide-3 Kinase Inhibitors
  • MAP Kinase Kinase 1