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

December 2013 in “ Molecular cancer therapeutics ”

Yu Wang, Qi Yu, Xin He, Todd Romigh, Jessica Altemus, Charis Eng

androgen receptor AR NVP-BEZ235 PI3K/mTOR inhibitor PTEN KLLN dihydrotestosterone DHT

TLDR Breast cancer treatments work better with AR activation, improving results and reducing side effects.

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.

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