Genomic profiling defines subtypes of prostate cancer with the potential for therapeutic stratification

The remarkable variation in prostate cancer clinical behavior represents an opportunity to identify and understand molecular features that can be used to stratify patients into clinical subgroups for more precise outcome prediction and treatment selection. Significant progress has been made in recent years in establishing the composition of genomic and epigenetic alterations in localized and advanced prostate cancers using array-based technologies and next-generation sequencing approaches. The results of these efforts shed new light on our understanding of this disease and point to subclasses of prostate cancer that exhibit distinct vulnerabilities to therapeutics. The goal of this review is to categorize the genomic data and, where available, corresponding expression, functional, or related therapeutic information, from recent large-scale and in-depth studies that show a new appreciation for the molecular complexity of this disease. We focus on how these results inform our growing understanding of the mechanisms that promote genetic instability, as well as routes by which specific genes and biologic pathways may serve as biomarkers or potential targets for new therapies. We summarize data that indicate the presence of genetic subgroups of prostate cancers and show the high level of intra- and intertumoral heterogeneity, as well as updated information on disseminated and circulating tumor cells. The integrated analysis of all types of genetic alterations that culminate in altering critical biologic pathways may serve as the impetus for developing new therapeutics, repurposing agents used currently for treating other malignancies, and stratifying early and advanced prostate cancers for appropriate interventions.