biostudies-literatureUnknown15Yu EMProstate cancer is the most common non-cutaneous cancer among American men. Multiple mechanisms are involved in tumorigenesis and progression to metastases. While androgen deprivation therapy remains the cornerstone of treatment, progression to castration-resistant disease becomes inevitable. Aberrant pathway activations of PI3K/AKT due to PTEN loss, epithelial-mesenchymal transition pathways, homologous recombination repair, and DNA repair pathway mechanisms of resistance and cross-talk lead to opportunities for therapeutic targeting in metastatic castration-resistant prostate cancer. This review focuses on mechanisms of progression and key trials that evaluate the drugs and combinations that exploit these pathways.Research and reports in urology519-529https://www.ebi.ac.uk/biostudies/studies/S-EPMC10693764biostudies-literatureMechanistic Insights on Localized to Metastatic Prostate Cancer Transition and Therapeutic Opportunities.PMC10693764Hwang MWYu EMAragon-Ching JBfalseMechanistic Insights on Localized to Metastatic Prostate Cancer Transition and Therapeutic Opportunities.Prostate cancer is the most common non-cutaneous cancer among American men. Multiple mechanisms are involved in tumorigenesis and progression to metastases. While androgen deprivation therapy remains the cornerstone of treatment, progression to castration-resistant disease becomes inevitable. Aberrant pathway activations of PI3K/AKT due to PTEN loss, epithelial-mesenchymal transition pathways, homologous recombination repair, and DNA repair pathway mechanisms of resistance and cross-talk lead to opportunities for therapeutic targeting in metastatic castration-resistant prostate cancer. This review focuses on mechanisms of progression and key trials that evaluate the drugs and combinations that exploit these pathways.2023-01-01T00:00:00Z20232025-04-25T17:25:14.911Z2025-04-06T04:05:33.644ZS-EPMC106937643805058710.2147/RRU.S386517