Quo vadis: Advanced prostate cancer—clinical care and clinical research in the era of multiple androgen receptor‐directed therapies

  title={Quo vadis: Advanced prostate cancer—clinical care and clinical research in the era of multiple androgen receptor‐directed therapies},
  author={Won Seog Kim and Charles J. Ryan},
The novel androgen receptor‐directed therapies abiraterone acetate and enzalutamide, having demonstrated improved survival in randomized phase 3 studies of men with metastatic castration‐resistant prostate cancer, have ushered in a new era in the treatment of this disease. Additional novel androgen receptor‐directed therapies, such as ARN‐509 and orteronel, are in various phases of clinical trials and development. However, the emergence of therapeutic resistance and clinical disease progression… 
Phase I and II therapies targeting the androgen receptor for the treatment of castration resistant prostate cancer
Except for the development of novel antiandrogens and CYP-17 modulators, bipolar androgen therapy is an interesting therapeutic approach and the combinations of the novel agents tested in Phase I and II studies with established agents is another field of interest.
Androgen–glucocorticoid interactions in the era of novel prostate cancer therapy
Understanding the biological role of glucocorticoid-related mechanisms that can cause iatrogenic stimulation of prostate cancer growth have emerged, which might contribute to drug resistance and disease progression despite optimal ADT.
Molecular landscape of prostate cancer: implications for current clinical trials.
Sipuleucel-T and Androgen Receptor-Directed Therapy for Castration-Resistant Prostate Cancer: A Meta-Analysis
Treatment with sipuleucel-T and AR-directed therapies significantly improved overall survival in patients with CRPC and improved time-to-progression and reduction of PSA level ≥50%.
Sequential maximum androgen blockade (MAB) in minimally symptomatic prostate cancer progressing after initial MAB: two case reports
Evidence of sustained biochemical response in two patients following second- and third-line MAB using rechallenge schedule of previously administered anti-androgen after latent interval is observed.
Discovery and development of Galeterone (TOK-001 or VN/124-1) for the treatment of all stages of prostate cancer.
This drug annotation summarizes the mechanisms of action, scientific rationale, medicinal chemistry, pharmacokinetic properties, and human efficacy data for galeterone, which has successfully completed phase II clinical development in men with castration resistant (advanced) prostate cancer (CRPC).
Isoflavones and Prostate Cancer: A Review of Some Critical Issues
Isoflavones play a protective role against the development ofPCa, however, careful consideration should be given when isoflavones are used in the prevention and treatment of PCa.
Isoflavones of Soy: Chemistry and Health Benefits


ARN-509: a novel antiandrogen for prostate cancer treatment.
ARS-509 exhibits characteristics predicting a higher therapeutic index with a greater potential to reach maximally efficacious doses in man than current AR antagonists, and offers preclinical proof of principle for ARN-509 as a promising therapeutic in bothCastration-sensitive and castration-resistant forms of prostate cancer.
ARN-509 in men with metastatic castration-resistant prostate cancer (mCRPC).
  • E. Antonarakis, N. Shore, H. Scher
  • Medicine
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • 2013
Post-AA data suggests that ARN-509 has activity in a subset of patients that developed resistance to abiraterone acetate, with robust PSA response in the tx-naïve cohort, with safe and well tolerated results in men with mCRPC.
AZD3514: A Small Molecule That Modulates Androgen Receptor Signaling and Function In Vitro and In Vivo
The biological characterization of AZD3514 is described, an orally bioavailable drug that inhibits androgen-dependent and -independent AR signaling and shows antitumor activity in the HID28 mouse model of CRPC in vivo.
Phase I clinical trial of a selective inhibitor of CYP17, abiraterone acetate, confirms that castration-resistant prostate cancer commonly remains hormone driven.
  • G. Attard, A. Reid, J. D. de Bono
  • Medicine, Biology
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • 2008
CYP17 blockade by abiraterone acetate is safe and has significant antitumor activity in CRPC, and data confirm that CRPC commonly remains dependent on ligand-activated AR signaling.
Phase I clinical trial of the CYP17 inhibitor abiraterone acetate demonstrating clinical activity in patients with castration-resistant prostate cancer who received prior ketoconazole therapy.
  • C. Ryan, Matthew R. Smith, E. Small
  • Medicine, Biology
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • 2010
Abiraterone acetate was well tolerated and demonstrated activity in CRPC, including in patients previously treated with ketoconazole, and continued clinical study is warranted.
Abiraterone and increased survival in metastatic prostate cancer.
The inhibition of androgen biosynthesis by abiraterone acetate prolonged overall survival among patients with metastatic castration-resistant prostate cancer who previously received chemotherapy.
Enzalutamide in metastatic prostate cancer before chemotherapy.
Enzalutamide significantly decreased the risk of radiographic progression and death and delayed the initiation of chemotherapy in men with metastatic prostate cancer.