Clinical meaning
Prostate cancer pathogenesis involves a multistep process from prostatic intraepithelial neoplasia (PIN) to invasive adenocarcinoma. Key molecular alterations include TMPRSS2-ERG gene fusion (found in ~50% of prostate cancers), loss of PTEN tumor suppressor, TP53 mutations (associated with castration resistance), and androgen receptor amplification/mutation. The androgen receptor (AR) signaling axis is the central therapeutic target: testosterone is converted to dihydrotestosterone (DHT) by 5-alpha reductase, and DHT binds AR to activate transcription of proliferative genes. Castration-resistant prostate cancer (CRPC) develops through AR amplification, AR splice variants (AR-V7), intratumoral androgen synthesis, and bypass signaling pathways. The clinician must apply risk stratification (NCCN guidelines), prescribe stage-appropriate therapy across the spectrum from active surveillance to combination systemic therapy, manage treatment toxicities, and integrate genomic testing into clinical decision-making.