Activation of PI3K/Akt/mTOR signaling in the tumor stroma drives endocrine therapy-dependent breast tumor regression

• DOI: 10.18632/oncotarget.4203
• Publication Date: 2015-09-15T04:47:30Z
• Authors: María Laura Polo; Marina Riggio; María May; María Jimena Rodr...; María Cecilia Per...; Melody Stallings-...; Diego Kaen; Marlene Frost; Matthew Goetz; Judy Boughey; Claudia Lanari; Derek Radisky; Virginia Novaro
• Keywords: Neoadjuvant Therapy

Improved efficacy of neoadjuvant endocrine-targeting therapies in luminal breast carcinomas could be achieved with optimal use pathway targeting agents. In a mouse model ductal carcinoma we identify tumor regressive stromal reaction that is induced by endocrine therapy. This reparative characterized neovascularization accompanied infiltration immune cells and carcinoma-associated fibroblasts stain for phosphorylated ribosomal protein S6 (pS6), downstream the PI3K/Akt/mTOR pathway. While variants higher activity respond well to combination inhibitors, lower more poorly therapy than alone, associated inhibition pS6 reaction. human cancer xenografts confirm such differential sensitivity primarily determined level cells. We further show clinical response patients undergoing conclude localization are therapeutic represent biomarkers distinguish which tumors will benefit from incorporation inhibitors