Prostate cancer genotyping for risk stratification and precision treatment

Abstract

Prostate cancer (PC) is the most frequently diagnosed cancer and second leading cause of cancer-related deaths in men. It is heterogeneous, as is evident from the wide spectrum of therapeutic approaches. Most patients with PC are initially responsive to androgen deprivation therapy; however, the majority of cases are either hormone-sensitive PC or castration-resistant PC. Current therapeutic protocols follow the evolution of PC, a continuously progressive process involving a combination of widespread genomic alterations. These genomic alterations are either hereditary germline mutations, such as mutations in BRCA2, or specific only to tumor cells (somatic). Tumor-specific genomic spectra include genomic structural rearrangements, canonical androgen response genes, and many other specific genes such as TMPRSS2-ERG fusion, SPOP/FOXA1, TP53/RB1/PTEN, and BRCA2. New evidence indicates the involvement of signaling pathways including PI3K, WNT/β-catenin, SRC, and IL-6/STAT, which have been shown to promote epithelial-mesenchymal transition cancer stem cell-like features/stemness, and neuroendocrine differentiation in PC. Over the last decade, our understanding of the genotype-phenotype relationships has been enhanced considerably. The genetic background of PC related to canonical genetic alterations and signaling pathway activation genes has shed more insight into the molecular subtype and disease landscape, resulting in a more flexible role of individual therapies targeting diverse genotypes and phenotypes.

Keywords

Prostate cancer / Prostate cancer treatment / Prostate cancer genomics / Hereditary prostate cancer / Androgen deprivation therapy / Hormone sensitive prostate cancer / Kinase signaling

Acknowledgments

None.

Statement of ethics

Not applicable.

Conflict of interest statement

No conflict of interest has been declared by the author.

Funding source

None.

Author contributions

Author contributed to paper in entirety.

Data Availability

The datasets generated during and/or analyzed during the current study are not publicly available, but are available from the corresponding author on reasonable request.

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