New targets for resistant prostate cancer.

Timothy C Thompson,Likun Li

doi:10.18632/oncotarget.2544

Abstract

New targets for resistant prostate cancer.

Highlights

Prostate cancer (PCa) initially responds to standard luteinizing hormone releasing hormone agonist–based androgen-deprivation therapy (ADT), most advanced, lethal prostate cancer (PCa) eventually becomes castrationresistant PCa (CRPC) and metastasizes to bone [1]
The authors demonstrated that specific genes related to DNA metabolism, DNA synthesis and repair, androgen metabolism, and the cell cycle are repressed by active androgen receptor (AR) and derepressed by antiAR agents [5]
Intratumoral synthesis of androgens was shown to lead to partial restoration of AR transcriptional activity in CRPC, yet these androgen levels were not sufficient to downregulate the expression of specific AR-repressed genes related to the cell cycle, DNA synthesis and repair, and DNA metabolism [5]

Summary

Introduction

Prostate cancer (PCa) initially responds to standard luteinizing hormone releasing hormone agonist–based androgen-deprivation therapy (ADT), most advanced, lethal PCa eventually becomes castrationresistant PCa (CRPC) and metastasizes to bone [1]. The fact that mutations cause persistent AR signaling has long been understood, suppression of AR signaling through pharmacologic inhibition was only recently shown to lead to derepression of specific oncogenic signaling pathways in PCa. Carver et al demonstrated that ADT or treatment with ENZ increased the phosphorylation of Akt in PTEN-deleted LNCaP cells and LAPC4 cells, whereas the combination of ENZ and BEZ235, a PI3K inhibitor, caused marked regression of

Results

Conclusion