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Review
. 2014 Jun 3;10(6):596-601.
doi: 10.7150/ijbs.8780. eCollection 2014.

Roles for the backdoor pathway of androgen metabolism in prostate cancer response to castration and drug treatment

Michael V Fiandalo  1 , John Wilton  1 , James L Mohler  1
Affiliations
Review

Roles for the backdoor pathway of androgen metabolism in prostate cancer response to castration and drug treatment

Michael V Fiandalo et al. Int J Biol Sci. .

Abstract

Almost all men who present with advanced prostate cancer (CaP) and many men who fail potentially curative therapy are treated with androgen deprivation therapy (ADT). ADT is not curative and CaP recurs as the lethal phenotype. The goal of this review is to describe the evolution of adrenal androgen blockade, how new androgen measurement methods have furthered understanding of androgen metabolism, and how further understanding of the backdoor pathway of androgen metabolism may lead to interventions that extend survival even more.

Keywords: "Backdoor" Pathway; Adrenal androgens; CYP17A1.; Dihydrotestosterone; Prostate cancer.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interest exists.

Figures

Figure 1
Figure 1
Four androgen metabolism pathways to DHT synthesis. Pathway 1 is the 5α-reduction of T to DHT (dashed lines). Pathway 2 uses adrenal androgens, DHEA or ASD, to synthesize T or 5α-dione that are converted to DHT (faint gray long dashes). Pathway 3 is the cholesterol pathway (small gray dashes). Pathway 4 is the backdoor pathway of DHT synthesis using androstanediol instead of T to generate DHT (outlined in bold). Abiraterone inhibits 17α-hydroxylase and 17,20-lyase of CYP17A1 (relevant to Pathways 2 and 4) whereas TAK-700 or TOK-001 inhibit only 17,20-lyase (relevant to Pathway 2).
See this image and copyright information in PMC

References

    1. Huggins C, Hodges CV. Studies on prostatic cancer: I. The effect of castration, of estrogen and androgen injection on serum phsphatases in metastatic carcinoma of prostate. Cancer Res. 1941;1:293–297. - PubMed
    1. Huggins C, Scott WW. Bilateral adrenalectomy in prostatic cancer: clinical features and urinary excretion of 17-ketosteroids and estrogen. Ann Surg. 1945;122:1031–1041. - PMC - PubMed
    1. Thorn GW, Forsham PH, Frawley TF. et al. The clinical usefulness of ACTH and cortisone. N Engl J Med. 1950;242:865–872. - PubMed
    1. Huggins C, Bergenstal DM. Surgery of the adrenals. J Am Med Assoc. 1951;147:101–106. - PubMed
    1. Harrison JH, Thorn GW, Jenkins D. Total adrenalectomy for reactivated carcinoma of the prostate. N Engl J Med. 1953;248:86–92. - PubMed