The Androgen Receptor (AR) pathway is a primary target for metastatic castration-resistant prostate cancer (mCRPC) treatment, and AR blockade with enzalutamide is a well-established therapeutic option for targeting the AR pathway in mCRPC. However, prostate cancer cells can bypass AR blockades through induction of other pathways for survival, and recently numerous preclinical studies have made the PI3K-AKT pathway a target of interest for the treatment of drug-resistant mCRPC. The PI3K-AKT pathway has pleiotropic effects, and its inhibition has long been of interest in the management of prostate cancer. We previously reported that AKT inhibition (Ipatasertib) significantly decreases cell proliferation, increases canonical AR activity, and remodels the chromatin landscape in vitro and in vivo . However, the effects of AKT inhibition on chromatin accessibility remain poorly understood. This study aims to assess chromatin landscape modifications under PI3K-AKT pathway inhibition. In this study, LuCaP 167 patient-derived organoid (PDO) models were treated with AKT inhibitors (Ipatasertib and MK2206), and the chromatin landscape was studied using ATAC-seq. Preliminary results reveal that both Ipatasertib and MK2206 significantly altered chromatin accessibility in LuCaP 167 PDO compared with the non-treated control group. Interestingly, footprinting and motif analysis revealed several transcription factor motifs enriched by AKT inhibition, including KLF15, a tumor suppressor. While the results are preliminary, our data provide additional insights into AKT's influence on chromatin accessibility.