Localized prostate cancer genotyping: another step towards personalized therapy

Abstract

Prostate cancer (PCa) is marked by a broad heterogeneous spectrum of clinical behavior, ranging from indolent subclinical forms up to aggressive metastatic and rapidly lethal tumors. This complex landscape of PCa behavior denotes the extreme genomic heterogeneity of this tumor type (1). Interestingly, the genomic heterogeneity of PCa is observed not only between the primary (localized) tumor and the advanced (metastatic) tumor samples, but also within each of the two disease stages. Certainly, PCa molecular characterization could provide an important impact in defining the patients’ prognosis and guiding therapeutic decisions. In this light, a pivotal contribution in understanding localized PCa molecular taxonomy comes from the whole exome sequencing molecular analysis of more than 300 primary PCa performed by the Cancer Genome Atlas (TCGA) study group (2). This analysis confirmed the androgenic dependence of primary PCa, the significant incidence (about a quarter) of activating mutations of the phosphoinositide 3-kinase (PI3K)/Akt/mTOR and MAPK signaling pathways, and the possibility to classify the vast majority of PCa tumors into seven subtypes defined by specific gene fusions (ERG, ETV1/4, and FLI1) or recurrent mutations in specific genes (SPOP, FOXA1, and IDH1) (2).