Androgens in prostate cancer: A tale that never ends

Androgens play an essential role in prostate cancer. Clinical treatments that target steroidogenesis and the androgen receptor (AR) successfully postpone disease progression. Abiraterone and enzalutamide, the next-generation androgen receptor pathway inhibitors (ARPI), emphasize the function of the androgen-AR axis even in castration-resistant prostate cancer (CRPC). However, with the increased incidence in neuroendocrine prostate cancer (NEPC) showing resistance to ARPI, the importance of androgen-AR axis in further disease management remains elusive. Herein we review the steroidogenic pathways associated with different disease stages and discuss the potential targets for disease management after manifesting resistance to abiraterone and enzalutamide. •The steroidogenic pathways in prostate cancer cells are accommodated to different clinical treatments.•Steroidogenic enzymes are promising targets for further disease treatment.•Supraphysiological testosterone is another innovative strategy to treat prostate cancer.