Tijdschrift voor Urologie

, Volume 2, Issue 2, pp 22–28

De theoretische achtergrond van de nieuwe behandelingen bij castratieresistent prostaatcarcinoom (CRPC)

  • A. N. Vis
Article
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Samenvatting

De kennis van de cellulaire, biochemische, moleculaire en/of genetische mechanismen die optreden tijdens de overgang van ‘hormoon-naïef ’ naar castratieresistent prostaatcarcinoom (CRPC) neemt snel toe. Deze kennis schept de mogelijkheid om in te spelen op de toekomstige ontwikkeling van medicijnen, en op de behandeling van patiënten in deze potentieel fatale fase van de ziekte. In dit overzichtsartikel worden de mechanismen beschreven die prostaatcarcinoomcellen gebruiken om de voor hen ongunstige condities van androgeendeprivatie door medische of chirurgische castratie te omzeilen, om hun groeivoordeel te behouden. In CRPC maken prostaatcarcinoomcellen nog vaak gebruik van androgeengereguleerde processen die lopen via de androgeenreceptor. Zo gebruiken zij androgenen afkomstig uit de circulatie efficiënter door veranderde genexpressie, en door een hernieuwde en verhoogde expressie van steroïdconverterende enzymen.

Summary

The theoretical background of new treatments of castration resistant prostate cancer (CRPC)

Knowledge of the molecular, cellular and genetic changes that occur during the transition of hormone-naïve to castrationresistant prostate cancer (CRPC) is increasing rapidly. This might provide a window of opportunity for (future) drug development, and for treating patients with these potential devastating states of disease. The objective of this review is to provide an understanding of the mechanisms that prostate cancer cells use to bypass androgen-deprived conditions. In CRPC, prostate cancer cells still rely on intracellular androgens and on an activeandrogen receptor for growth and survival. CRPC’s have gained mechanisms that enable them to use steroids from the circulation more efficiently through altered gene expression, and through a renewed and upregulated synthesis of steroid hormone-converting enzymes.

Keywords

Prostate cancer Androgens Castration Resistance Treatment 

Trefwoorden

prostaatcarcinoom androgenen castratie resistentie behandeling 

Literatuur

  1. 1.
  2. 2.
    Huggins C, Hodges CV. Studies on prostatic cancer. I. The effect of castration, of estrogen and androgen injection on serum phosphatases in metastatic carcinoma of the prostate. Cancer Res. 1941;1:293–7.Google Scholar
  3. 3.
    Lubahn DB, Joseph DR, Sullivan PM, et al. Cloning of human androgen receptor complementary DNA and localization to the X chromosome. Science. 1988;240:327–30.PubMedCrossRefGoogle Scholar
  4. 4.
    Gelman EP. Molecular biology of the androgen receptor. J Clin Oncol. 2002;13:3001–15.CrossRefGoogle Scholar
  5. 5.
    Lucas A, Petrylak DP. The case for early chemotherapy for thetreatment of of metastatic disease. J Urol. 2006;176;S72–5.PubMedCrossRefGoogle Scholar
  6. 6.
    Palmberg C, Koivisto P, Kakkola L, et al. Androgen receptor gene amplification at primary progression predicts response to combined androgen blockade as second line therapy for advanced prostate cancer. J Urol. 2000;164:1992–5.PubMedCrossRefGoogle Scholar
  7. 7.
    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.PubMedCrossRefGoogle Scholar
  8. 8.
    Ettinger SL, Sobel R, Whitmore TG, et al. Dysregulation of sterol response element-binding proteins and downstream effectors in prostate cancer during progression to androgen independence. Cancer Res. 2004;64:2212–21.PubMedCrossRefGoogle Scholar
  9. 9.
    Feldman BJ, Feldman D. The development of androgenindependent prostate cancer. Nat Rev. 2001;1:34–45.CrossRefGoogle Scholar
  10. 10.
    Balk SP. Androgen receptor as a target treatment in androgenindependent prostate cancer. Urology. 2002;60 (Suppl 3A):132–9.PubMedCrossRefGoogle Scholar
  11. 11.
    Vis AN, Schröder FH. Key targets of hormonal treatment of prostate cancer. Part 1: the androgen receptor and steroidogenic pathways. BJU Int. 2009;104:438–48.PubMedCrossRefGoogle Scholar
  12. 12.
    Gregory CW, He B, Johnson RT, et al. A mechanism for androgen receptor-mediated prostate cancer recurrence after androgen deprivation therapy. Cancer Res. 2001;61:4315–9.PubMedGoogle Scholar
  13. 13.
    Bruchovsky N, Klotz LH, Sadar M, et al. Intermittent androgen suppression for prostate cancer: Canadian Prospective Trial and related observations. Mol Urol. 2000;4:191–9.PubMedGoogle Scholar
  14. 14.
    Gregory CW, Johnson RT, Mohler JL, et al. Androgen receptor stabilization in recurrent prostate cancer is associated with hypersensitivity to low androgen. Cancer Res. 2001;61:2892–8.PubMedGoogle Scholar
  15. 15.
    Labrie F, Dupont A, Bélanger A, et al. Treatment of prostate cancer with gonadotropin-releasing hormone agonists. Endocr Rev. 1986;7:67–74.PubMedCrossRefGoogle Scholar
  16. 16.
    de Jong FH, Reuvers PJ, Bolt-de Vries J, et al. Androgens and androgen-receptors in prostate tissue from patients with benign prostatic hyperplasia: effects of cyproterone acetate. J Steroid Biochem Mol Biol. 1992;42:49–55.PubMedCrossRefGoogle Scholar
  17. 17.
    Scher HI, Kelly WK. Flutamide withdrawal syndrome: its impact on clinical trials in hormone-refractory prostate cancer. J Clin Oncol. 1993;11:1566–72.PubMedGoogle Scholar
  18. 18.
    Heracek J, Richard H, Martin H, et al. Tissue and serum levels of principal androgens in benign prostatic hyperplasia and prostate cancer. Steroids. 2007;72:375–80.PubMedCrossRefGoogle Scholar
  19. 19.
    Marks LS, Mostaghel EA, Nelson PS. Prostate tissue androgens: history and current clinical relevance. Urology. 2008;72:247–54.PubMedCrossRefGoogle Scholar
  20. 20.
    Marks LS, Mazer NA, Mostaghel E, et al. Effect of testosterone replacement therapy on prostate tissue in men with lateonset hypgonadism: a randomized controlled trial. JAMA. 2006;196:2351–61.CrossRefGoogle Scholar
  21. 21.
    Page ST, Lin DW, Mostaghel EA, et al. Persistent intraprostatic androgen concentrations after medical castration in healthy men. J Clin Endocrinol Metab. 2006;91:3850–6.PubMedCrossRefGoogle Scholar
  22. 22.
    Locke JA, Guns ES, Lubik AA, et al. Androgen levels increase by intratumoral de novo steroidogenesis during progression of castration-resistant prostate cancer. Cancer Res. 2008;68:6407–15.PubMedCrossRefGoogle Scholar
  23. 23.
    Montgomery RB, Mostaghel EA, Vessella, et al. Maintenance of intratumoral androgens in metastatic prostate cancer : a mechanism for castration-resistant tumor growth. Cancer Res. 2008;68:4447–54.PubMedCrossRefGoogle Scholar
  24. 24.
    Titus MA, Schell MJ, Lih FB, et al. Testosterone and dihydrotestosterone tissue levels in recurrent prostate cancer. Clin Cancer Res. 2005;11:4653–7.PubMedCrossRefGoogle Scholar
  25. 25.
    Ji Q, Chang L, Stanczyk FK, et al. Impaired dihydrotestosterone catabolism in human prostate cancer: critical role of AKR1C2 as a pre-receptor regulator of androgen receptor signaling. Cancer Res. 2007;67:1361–9.PubMedCrossRefGoogle Scholar
  26. 26.
    Geller J. Effect of finasteride, a 5 alpha-reductase inhibitor on prostate tissue androgens and prostate-specific antigen. J Clin Endocrinol Metab. 1990;71:1552–5.PubMedCrossRefGoogle Scholar
  27. 27.
    Nishiyama T, Hashimoto Y, Takahashi K. The influence of androgen deprivation therapy on dihydrotestosterone levels in the prostatic tissue of patients with prostate cancer. Clin Cancer Res. 2004;10:7121–6.PubMedCrossRefGoogle Scholar
  28. 28.
    Mohler JL, Gregory CW, Ford OH 3rd, et al. The androgen axis in recurrent prostate cancer. Clin Cancer Res. 2004;10:440–8.PubMedCrossRefGoogle Scholar
  29. 29.
    van der Sluis TM, Vis AN, Moorselaar RJ van, et al. Intraprostatic testosterone and dihydrotestosterone. Part I: Methods of determination and concentrations in men with benign prostatic hyperplasia and prostate cancer. Submitted.Google Scholar
  30. 30.
    van der Sluis TM, Meuleman EJ, Moorselaar RJ van, et al. Intraprostatic testosterone and dihydrotestosterone. Part II: Concentrations after androgen hormonal manipulation in men with benign prostatic hyperplasia and prostate cancer. Submitted.Google Scholar
  31. 31.
    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.PubMedCrossRefGoogle Scholar
  32. 32.
    Fung K-M, Samara ENS, Wong C, et al. Increased expression of type 2 3-alpha-hydroxysteroid dehydrogenase/type 5 17betahydroxysteroid dehydrogenease (AKR1C3) and its relationship with androgen receptor in prostatic adenocarcinoma. Endocrine-Related Cancer. 2006;13:169–80.PubMedCrossRefGoogle Scholar
  33. 33.
    Vis AN, Schröder FH. Key targets of hormonal treatment of prostate cancer. Part 2: The androgen receptor and 5alphareductase. BJU Int. 2009;104:1191–7.PubMedCrossRefGoogle Scholar
  34. 34.
    de Bono JS, Logothetis CJ, Molina A, et al. Abiraterone and increased survival in metastatic prostate cancer. New Engl J Med. 2011;364:1995–2005.PubMedCrossRefGoogle Scholar
  35. 35.
    Mizokami A, Koh E, Fujita H, et al. The adrenal androgen androstenediol is present in prostate cancer tissue after androgen deprivation therapy and activates mutated androgen receptor. Cancer Res. 2004;64:765–71.PubMedCrossRefGoogle Scholar
  36. 36.
    Isaacs JT. The biology of hormone refractory prostate cancer. Why does it develop. Urol Clin North Am. 1999;26:263–73.PubMedCrossRefGoogle Scholar
  37. 37.
    Craft N, Chhor C, Tran C, et al. Evidence for clonal outgrowth of androgen-independent prostate cancer cells from androgendependent tumors through a two-step process. Cancer Res. 1999;59:5030–6.PubMedGoogle Scholar

Copyright information

© Bohn Stafleu van Loghum 2012

Authors and Affiliations

  • A. N. Vis
    • 1
  1. 1.afdeling UrologieVrije Universiteit medisch centrumAmsterdamThe Netherlands

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