Dual PI3K and Wnt pathway inhibition is a synergistic combination against triple negative breast cancer

Abstract

Therapeutics: Dual therapy shrinks triple negative breast tumors Two experimental drugs currently in clinical trials as single agents might work better together against triple negative breast cancer. Jeffrey Solzak and Milan Radovich, and colleagues from the Indiana University School of Medicine in Indianapolis, USA, analyzed gene expression data from cancerous and healthy breast tissues and from published genomic datasets. They found the PI3K pathway consistently activated in the majority of breast cancers that test negative for the three most common receptors known to fuel breast tumor growth. Inhibiting PI3K in these cells led to a marked increase in the activity of another critical pathway called Wnt, an observation that prompted the researchers to test a combination of a PI3K inhibitor, buparlisib, and a Wnt inhibitor, WNT974, in cell lines and xenograft models. Tumor cells shrunk more and mice lived longer than treatment with either agent alone.