Activation of Androgen Receptor Sensitizes Breast Carcinomas to NVP-BEZ235's Therapeutic Effect Mediated by PTEN and KLLN Upregulation

The study concluded that activation of the androgen receptor (AR) sensitized breast carcinomas to the therapeutic effects of NVP-BEZ235, a dual PI3K/mTOR inhibitor, through the upregulation of tumor suppressors PTEN and KLLN. AR-positive breast cancer cells showed increased sensitivity to NVP-BEZ235, and reintroducing AR in AR-negative cells restored this sensitivity. The combination of dihydrotestosterone (DHT) with NVP-BEZ235 enhanced growth inhibition and tumor regression in AR+/ER+ tumors, suggesting that AR activation could improve therapeutic outcomes and serve as a predictive biomarker for NVP-BEZ235 response in breast cancer treatment.