Evasion of targeted cancer therapy through stem-cell-like reprogramming.

Prostate cancer variants expressing alternative lineage markers appear at relapse from antiandrogen therapy. We show that loss of the retinoblastoma ( RB1 ) and tumor protein 53 ( TP53 ) genes drives expression of stem cell reprogramming factors, lineage plasticity, and antiandrogen resistance. Epigenetic manipulation restores antiandrogen sensitivity-suggesting an approach for treating lethal prostate cancers.