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Eventually cancer cells can grow resistant to this treatment. This most-advanced stage of the disease, called castration-resistant prostate cancer, is treated with continued hormone therapy alongside the chemotherapy drug docetaxel. Some tumors metastasize (spread) to other areas of the body, particularly the bones and lymph nodes.
Castration-resistant prostate cancer (CRPC) is prostate cancer that progresses despite extremely low testosterone in the body often due to medical castration. [4] Unlike many other types of prostate cancer, CRPC do not need normal testosterone levels, but they still require regular androgen receptors (AR).
The PI3K pathway is a major source of drug resistance in prostate cancer. This is particularly true in castration-resistant prostate cancer, where tumours become resistant to androgen-deprivation therapy, which block the tumours ability to utilise the hormone androgen to grow. [17]
Prostate cancer predominantly occurs in the peripheral zone of the human prostate, with fewer than 10% of cases found in the central zone. The disease develops as a result of the temporal and spatial loss of the basal epithelial compartment as well as increased proliferation and dedifferentiation of the luminal (secretory) epithelial cells.
Cancer Stem Cell phenotypes are associated with disease recurrence, metastasis, and cell survival in circulation as Circulating tumor cells. Thus, activation of these programs via inhibition of the androgen axis provides a mechanism by which tumor cells can adapt to promote disease recurrence and progression.
Abiraterone acetate was FDA approved in April 2011 for treatment of castration-resistant prostate cancer for patients who have failed docetaxel therapy. Abiraterone acetate inhibits an enzyme known as CYP17, which is used in the body to produce testosterone.
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