Lam HM, Nguyen HM, Labrecque MP, et al. - A patient-derived xenograft (PDX) preclinical trial was conducted to distinguish key molecular phenotypes underlying supraphysiological testosterone (SPT) response to improve patient selection and guide combination treatment to achieve a durable response. This trial carried out with 13 castration-resistant prostate cancer (CRPC) PDXs to identify molecular features associated with SPT response. Researchers conducted comprehensive intratumoral androgen, tumor growth, and integrated transcriptomic and protein analyses in three PDXs resistant to the newer androgen receptor (AR) pathway inhibitor enzalutamide (ENZ) to determine SPT response and resistance. The data showed that SPT gives a durable response in AR-pathway inhibitor ENZ CRPC that is correlated with sustained suppression of ARv7 and E2F transcriptional outputs, and the DDR transcriptome, indicating the potential of combination treatments that maintain suppression of these programs to drive a durable response to SPT.