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

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.

• Authors: Brent N Rexer, Ritwik Ghosh, Carlos L Arteaga
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 15 Issue 14 Pg. 4518-20 (Jul 15 2009) ISSN: 1557-3265 [Electronic] United States
• PMID: 19584146 (Publication Type: Journal Article, Comment)

Chemical References

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

Topics

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