Mechanistic Insights on Localized to Metastatic Prostate Cancer Transition and Therapeutic Opportunities

Eun-mi Yu,1 Min Woo Hwang,2 Jeanny B Aragon-Ching1 1GU Medical Oncology, Inova Schar Cancer Institute, Fairfax, VA, USA; 2Department of Internal Medicine, Inova Fairfax Hospital, Fairfax, VA, USACorrespondence: Jeanny B Aragon-Ching, Clinical Program Director of Genitourinary Cancers, Inova Schar Cancer Institute, Associate Professor of Medical Education, University of Virginia School of Medicine, 8081 Innovation Park Drive, Fairfax, VA, USA, Tel +1-571-472-4724, Fax +1-571-472-1180, Email Jeanny.Aragon-Ching@inova.orgAbstract: 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.Keywords: prostate cancer, metastasis, castration-resistant prostate cancer, epithelial mesenchymal transition, androgen receptor pathway inhibitors, poly-ADP ribose pathway inhibitors