The AR splice variant AR-V7 is associated with resistance to enzalutamide and abiraterone21-23 and is also associated with increased AR CN.24 In addition to AR, alterations in other genes, including tumor protein p53 (TP53), phosphatase and tensin homolog (PTEN), and breast cancer gene 2 (BRCA2), are enriched in lethal prostate cancer.8-11 Studies support the idea that lineage plasticity from an AR-dependent to an AR-independent state through loss of TP53 and retinoblastoma-associated protein 1 (RB1) mediates resistance to AR-targeted therapies.25-28. This evidence concerns the gene PTEN and prostate cancer.