Integrative transcriptomic profiling reveals subtype-specific therapeutic vulnerabilities and resistance mechanisms in prostate cancer.

ABSTRACT:

Objective

Advanced prostate cancer (PCa) remains therapeutically challenging due to heterogeneous mechanisms of resistance to androgen receptor (AR)-targeting agents. While AR signaling persists in castration-resistant PCa (CRPC), emerging evidence suggests AR-independent survival pathways may contribute to therapeutic escape. This study integrates transcriptomic data and clinical profiling to dissect AR dependency and resistance mechanisms in PCa, aiming to identify subtype-specific vulnerabilities and therapeutic targets.

Methods

We performed CRISPR-Cas9 screens in AR-dependent (VCaP, LNCaP, 22Rv1) and AR-independent (DU145, PC-3, WPE1-NA22, P4E6, Shmac5) cell lines to identify core essential genes. RNA sequencing data from TCGA-PRAD, Changhai, and DKFZ cohorts were integr

SUBMITTER: Liu W 

PROVIDER: S-EPMC12822270 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature