Skip to main content
SpringerLink
Log in

Nieuwe hormonale manipulaties bij castratieresistent prostaatcarcinoom (CRPC)

  • Published:
Tijdschrift voor Urologie Aims and scope Submit manuscript

Samenvatting

Verschillende recente onderzoeken laten zien dat het castratieresistent prostaatcarcinoom (CRPC) nog steeds gevoelig is voor verdere beïnvloeding van de androgeenreceptor. Meerdere nieuwe therapieën hebben effectiviteit in de kliniek laten zien. Intracriene androgeenproductie en overexpressie van de androgeenreceptor zijn de belangrijkste veranderingen in CRPC-cellen. Fase 3-data met abiraterone acetaat en MDV3100, naast soortgelijke therapieën, bevestigen dat persisterende androgeen biosynthese en de androgeenreceptor in CRPC een goed doelwit zijn voor deze nieuwe vormen van hormonale manipulatie.

Summary

New hormonal manipulations in castration-resistant prostate cancer (CRPC)

Research over the past decade suggests that castration-resistant prostate cancer (CRPC) is sensitive to further manipulation of the androgen-androgen receptor (AR) axis. Several new therapies that target this axis have demonstrated clinical activity. Intracrine androgen production and AR amplification are the principal aberrancies driving CRPC growth. Phase III data with abiraterone acetate and MDV-3100, along with other similar therapies, confirm that the findings related to persistent AR signalling in a castrate milieu can be used to produce significant clinical benefit for patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Literatuur

  1. Cremers RGHM, Karim-Kos HE, Houterman S, et al. Prostate cancer: Trends in incidence, survival and mortality in the Netherlands, 1989-2006. Eur J Cancer. 2010;46:2077–87.

    Article  PubMed  CAS  Google Scholar 

  2. White JW. The results of double castration in hypertrophy of the prostate. Ann Surg. 1895;22:1–80.

    Article  PubMed  CAS  Google Scholar 

  3. Huggins C, Hodges CV. Studies on prostatic cancer. I. The effect of castration, of estrogen and of androgen injection on serum phosphatases in metastastic carcinoma of the prostate. Cancer Res. 1941;1:293–7.

    CAS  Google Scholar 

  4. Morote J, Orsola A, Planas J, et al. Redefining Clinically Significant Castration Levels in Patients With Prostate Cancer Receiving Continuous Androgen Deprivation Therapy. J Urol. 2007;178:1290–5.

    Article  PubMed  CAS  Google Scholar 

  5. Locke JA, Guns ES, Lubik AA. Androgen levels increase by intratumoral de novo steroidogenesis during progression of castration-resistant prostate cancer. Cancer Res. 2008;68:6407–15.

    Article  PubMed  CAS  Google Scholar 

  6. Mostaghel EA, Page ST, Lin DW, et al. Intraprostatic androgens and androgen-regulated gene expression persist after testosterone suppression: therapeutic implications for castration-resistant prostate cancer. Cancer Res. 2007;67:5033–41.

    Article  PubMed  CAS  Google Scholar 

  7. Stanbrough M, Bubley GJ, Ross K, et al. Increased expression of genes converting adrenal androgens to testosterone in androgenindependent prostate cancer. Cancer Res. 2006;66:2815–25.

    Article  PubMed  CAS  Google Scholar 

  8. Small EJ, Srinivas S. The antiandrogen withdrawal syndrome. Experience in a large cohort of unselected patients with advanced prostate cancer. Cancer. 1995;76:1428–34.

    Article  PubMed  CAS  Google Scholar 

  9. Ryan CJ, Tindall DJ. Androgen receptor rediscovered: the new biology and targeting the androgen receptor therapeutically. J Clin Oncol. 2011;29:3651–8.

    Article  PubMed  CAS  Google Scholar 

  10. Small EJ, Halabi S, Dawson NA. Antiandrogen withdrawal alone or in combination with ketoconazole in androgen-independent prostate cancer patients: a phase III trial (CALGB 9583). J Clin Oncol. 2004;22:1025–33.

    Article  PubMed  CAS  Google Scholar 

  11. Barrie SE, Potter GA, Goddard PM, et al. Pharmacology of novel steroidal inhibitors of cytochrome P450 17alpha (17-hydroxylase/ C17-20 lyase). J Steroid Biochem Mol Biol. 1994;50:267–73.

    Article  PubMed  CAS  Google Scholar 

  12. Pinto-Bazurco MAE, Negri M, Jagusch C, et al. Synthesis, biological evaluation, and molecular modeling of abiraterone analogues: Novel CYP17 inhibitors for the treatment of prostate cancer. J Med Chem. 2008;51:5009–18.

    Article  Google Scholar 

  13. Chen Y, Clegg NJ, Scher HI. Anti-androgens and androgendepleting therapies in prostate cancer: new agents for an established target. Lancet Oncol. 2009;10:981–91.

    Article  PubMed  Google Scholar 

  14. Sonpavde G, Attard G, Bellmunt J, et al. The role of abiraterone acetate in the management of prostate cancer: a critical analysis of the literature. Eur Urol. 2011;60:270–8.

    Article  PubMed  CAS  Google Scholar 

  15. Beltran H, Beer TM, Carducci MA, et al. New therapies for castration-resistant prostate cancer: efficacy and safety. Eur Urol. 2011;60:279–90.

    Article  PubMed  CAS  Google Scholar 

  16. De Bono JS, Logothetis CJ, Molina A, et al. Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med. 2011;364:1995–2005.

    Article  PubMed  Google Scholar 

  17. Logothetis C. Effect of abiraterone acetate (AA) on pain control and skeletal-related events (SRE) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) post docetaxel (D): Results from the COU-AA-301 phase III study. J Clin Oncol. 2011;29(15S):293s.

    Google Scholar 

  18. Agus DB. Safety, efficacy, and pharmacodynamics of the investigational agent TAK-700 in metastatic castration-resistant prostate cancer (mCRPC): Updated data from a phase I/II study. J Clin Oncol. 2011:29(15S):296s.

    Google Scholar 

  19. Attard G, Richards J, Bono JS de. New strategies in metastatic prostate cancer: targeting the androgen receptor signalling pathway. Clin Cancer Res. 2011;17:1649–57.

    Article  PubMed  CAS  Google Scholar 

  20. Tran C, Ouk S, Clegg NJ, et al. Development of a secondgeneration antiandrogen for treatment of advanced prostate cancer. Science. 2009;324:787–90.

    Article  PubMed  CAS  Google Scholar 

  21. Scher HI, Beer TM, Higano CS. Antitumour activity of MDV3100 in castration-resistant prostate cancer: a phase 1-2 study. Lancet. 2010;375:1437–46.

    Article  PubMed  CAS  Google Scholar 

  22. Bruno RD, Vasaitis TS, Gediya LK, et al. Synthesis and biological evaluations of putative metabolically stable analogs of VN/124- 1 (TOK-001): Head to head anti-tumor efficacy evaluation of VN/124-1 (TOK-001) and abiraterone in LAPC-4 human prostate cancer xenograft model. Steroids. 2011;76:1268–79.

    Article  PubMed  CAS  Google Scholar 

  23. Zoubeidi A, Zardan A, Beraldi E, et al. Cooperative Interactions between Androgen Receptor (AR) and Heat-Shock Protein 27 Facilitate AR Transcriptional Activity. Cancer Res. 2007;67:10455–65.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. afdeling Urologie, Vrije Universiteit medisch centrum, Amsterdam, The Netherlands

    R. J. A. van Moorselaar

Authors
  1. R. J. A. van Moorselaar
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

uroloog

Rights and permissions

Reprints and permissions

About this article

Cite this article

van Moorselaar, R.J.A. Nieuwe hormonale manipulaties bij castratieresistent prostaatcarcinoom (CRPC). Tijdschrift voor Urologie 2, 38–41 (2012). https://doi.org/10.1007/s13629-012-0009-1

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13629-012-0009-1

Trefwoorden

Search

Navigation