Molecular Mechanisms of Prostate Cancer Development in the Precision Medicine Era: A Comprehensive Review

Simple Summary Prostate cancer (PCa) is characterized by various genomic alterations that play a pivotal role in carcinogenesis. Efforts in precision medicine aimed at improving diagnosis, prevention, and surveillance based on genetic alterations are advancing. Notably, no tumor markers surpass prostate-specific antigen in specificity, and existing treatments primarily target the androgen receptor axis, with exceptions for patients with alterations in homologous recombination repair-related genes, such as BRCA1/2 and ATM, who may benefit from poly (ADP-ribose) polymerase inhibitors. In order to delineate the current state of research on PCa, we provide an overview of cutting-edge genomic research, including genome alterations, cancer immunology, and non-coding RNAs, in PCa. These aspects are relevant to comprehending the molecular mechanisms underlying health disparities, PCa initiation and progression, and drug resistance in the precision medicine era.Abstract The progression of prostate cancer (PCa) relies on the activation of the androgen receptor (AR) by androgens. Despite efforts to block this pathway through androgen deprivation therapy, resistance can occur through several mechanisms, including the abnormal activation of AR, resulting in castration-resistant PCa following the introduction of treatment. Mutations, amplifications, and splicing variants in AR-related genes have garnered attention in this regard. Furthermore, recent large-scale next-generation sequencing analysis has revealed the critical roles of AR and AR-related genes, as well as the DNA repair, PI3K, and cell cycle pathways, in the onset and progression of PCa. Moreover, research on epigenomics and microRNA has increasingly become popular; however, it has not translated into the development of effective therapeutic strategies. Additionally, treatments targeting homologous recombination repair mutations and the PI3K/Akt pathway have been developed and are increasingly accessible, and multiple clinical trials have investigated the efficacy of immune checkpoint inhibitors. In this comprehensive review, we outline the status of PCa research in genomics and briefly explore potential future developments in the field of epigenetic modifications and microRNAs.