Portal de Periódicos da CAPES

Transcriptional profiling identifies an androgen receptor activity-low, stemness program associated with enzalutamide resistance

2020; National Academy of Sciences; Volume: 117; Issue: 22 Linguagem: Inglês

10.1073/pnas.1922207117

1091-6490

Joshi J. Alumkal, Duanchen Sun, Eric Lu, Tomasz M. Beer, George Thomas, Emile Latour, Rahul Aggarwal, Jeremy Cetnar, Charles J. Ryan, Shaadi Tabatabaei, Shawna Bailey, Claire B. Turina, David A. Quigley, Xiangnan Guan, Adam Foye, Jack Youngren, Joshua A. Urrutia, Jiaoti Huang, Alana S. Weinstein, Verena Friedl, Matthew B. Rettig, Robert E. Reiter, Daniel E. Spratt, Martin Gleave, Christopher P. Evans, Joshua M. Stuart, Yiyi Chen, Felix Y. Feng, Eric J. Small, Owen N. Witte, Zheng Xia,

Radiopharmaceutical Chemistry and Applications

Significance The androgen receptor (AR) antagonist enzalutamide is one of the principal treatments for men with metastatic castration-resistant prostate cancer. However, not all patients respond, and de novo resistance mechanisms are largely unknown. To clarify mechanisms that contribute to enzalutamide resistance, we conducted a single-arm enzalutamide clinical trial. Metastatic tissue biopsies were required prior to study entry so we could attempt to identify molecular features associated with de novo resistance. Transcriptional profiling identified specific gene sets—including those linked to reduced AR transcriptional activity and a stemness program—that were activated in nonresponders. Our results suggest that patients whose tumors harbor this program should be considered for clinical trials testing rational agents to overcome de novo enzalutamide resistance.