In a mouse model, androgen deprivation treatment of some high-grade but stable prostate cancers accelerates their progression to invasive disease, according to an experimental study published online Cancer Discovery.

Shidong Jia, MD, PhD, of Harvard Medical School in Boston, and colleagues investigated the effect of androgen deprivation in a preclinical mouse model of high-grade prostatic intraepithelial neoplasia (HG-PIN) induced by the loss of the PTEN tumor suppressor.

The researchers found that surgical or chemical castration caused the stable HG-PIN to progress to invasive castration-resistant prostate cancer. Targeting the PI3K pathway pharmacologically or genetically reversed the PTEN-loss induced HG-PIN phenotype. Blocking both the PI3K pathway and the mitogen-activated protein kinase pathway blocked the growth of the castration-resistant prostate cancer.

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“Together, these data have revealed the potential adverse effects of anti-androgen chemoprevention in certain genetic contexts (such as PTEN loss) while showing the promise of targeted therapy in the clinical management of this complex and prevalent disease,” Dr. Jia’s group concluded.