New therapeutics settings in the treatment of castration resistant prostate cancer

Being able to predict which patients will develop metastasis and death with rising PSA levels after treatment with androgen ablation is essential for deciding therpeutic interventions and gauging prognosis. The major biologic processes under therpeutic investigation in prostate cancer involve growth and survival, chemotherapy and hormone therapy resistance, ex-tragonadal androgen production, modulation of the androgen receptor, angiogenesis, the bone interface, immune surveillance and escape, epigenetic regulation and stem cell renewal. A better understanding of this mechanisms responsible for prostate cancer growth and metastatic spread has allowed for the development of a wide array of new therapies.

The growth of prostate cancer is originally androgen dependent and metastatic tumors are generally treated with androgen ablation therapy, with or without antiandrogen supplementation [41, 42, 43]. However, resistance to hormonal therapy occurs within 12-18 months (remissions last on average 2-3 years, progression occurs even under castration [37, 44, 45], referred to as hormone-refractory or CRPC [41]. Resistance to hormones (in patients with metastatic disease) is probably shorter than 2-3 years, using PSA. Until recently, patients with castration-resistant prostate cancer had limited treatment options after docetaxel chemotherapy. However, in 2010, new options emerged [46]. The three nonhormonal systemic approaches that have been found to prolong survival are docetaxel as first line [4] chemotherapy, cabazitaxel as second-line cytotoxic chemotherapy [46, 47] and a vaccine named si-puleucel-T [48]. A new hormonal manipulation with abiraterone acetate [45] also showed to prolong survival in CRPC.

The current palliative treatment options for patients with CRPC can be divided in different groups such as secondary hormonal therapies, chemotherapy agents, vaccine-based immune therapy, bisphosphonates, radiotherapy and novel targets.

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