Genomic Profiling Defines Subtypes of Prostate Cancer with the Potential for Therapeutic Stratification

Considerations for targeted therapy based on key pathways perturbed in prostate cancer. Current standard of care involves active surveillance for low-risk localized prostate cancers; hormonal therapy, radical prostatectomy, or radiation therapy for higher-risk localized disease; and androgen pathway suppression for metastatic disease with chemotherapy and immunotherapy at the time of disease progression. This figure shows the potential for targeted therapy in molecularly defined subtypes of prostate cancer. Genomic alterations are classified on the basis of the class of molecular pathways affected (inner circle). Therapeutic agents (outer circle) targeting respective pathways are grouped with the genes (middle circle) commonly altered in these pathways, coordinated by color wherever possible. Selected agents in various phases of clinical trials are superscripted: ^aFDA-approved, ^bphase III clinical trials, ^cphase I/II clinical trials; preclinical development not marked. Although the antiandrogen therapy abiraterone, the microtubule inhibitor cabazitaxel, and the immunotherapy sipuleucel-T are already in clinical use, aberrations of NCOA2 and FOXA1 genes (white) are recent findings, the functional significance and therapeutic implications of which await further investigation. HDACi, histone deacetylase inhibitor.