Genomic profiling of prostate cancer: An updated review

Abstract

Understanding the genomic profiling of prostate cancer is crucial, owing to the emergence of precision medicine to guide therapeutic approaches. Over the last decade, integrative genomic profiling of prostate tumors has provided insights that improve the understanding and treatment of the disease. Minimally invasive liquid biopsy procedures have emerged to investigate cancer-related molecules with the advantage of detecting heterogeneity as well as acquired resistance in cancer. The metastatic castration-resistant prostate cancer (mCRPC) tumors have a highly complex genomic landscape compared to primary prostate tumors; a number of mCRPC harbor clinically actionable molecular alterations, including DNA damage repair (e.g., BRCA1/2 and ATM) and PTEN/phosphoinositide 3-kinase signaling. Heterogeneity in the genomic landscape of prostate cancer has become apparent and genomic alterations of TP53, RB1, AR, and cell cycle pathway are associated with poor clinical outcomes in patients. Prostate cancer with mutant SPOP shows a distinct pattern of genomic alterations, associating with better clinical outcomes. Several genomic profiling tests, which can be used in the clinic, are approved by the U.S. Food and Drug Administration, including MSK-IMPACT, FoundationOne CDx, and FoundationOne Liquid CDx. Here, we review emerging evidence for genomic profiling of prostate cancer, especially focusing on associations between genomic alteration and clinical outcome, liquid biopsy, and actionable molecular alterations.