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Pippione et al. Steroidogenic enzymes in prostate cancer

expression levels of certain steroidogenic enzymes Conflicts of interest
(SRD5A1, AKR1C2, AKR1C3, and HSD17B10) have There are no conflicts of interest.
been detected in a smaller number of bone metastases
when compared to non-malignant prostate and primary Patient consent
prostate tumor tissue [173] . Furthermore, in a recent Not applicable.
study AR amplification was not observed in bone
metastases from previously untreated PC patients, Ethics approval
but was detected in about half of metastatic samples Not applicable.
from patients with CRPC. This AR amplification was
associated with increased AR and AR-V7 expression REFERENCES
and a particularly poor prognosis [174] .
1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J
Steroidogenic enzymes are dependent on NAD/ Clin 2016;66:7-30.
NADH co-factor activity and hence better knowledge 2. Nelson PS, Clegg N, Arnold H, Ferguson C, Bonham M, White
of the Warburg effect in the bone microenvironment J, Hood L, Lin B. The program of androgen-responsive genes
might also be important. Additionally, enhanced in neoplastic prostate epithelium. Proc Natl Acad Sci U S A
understanding of how other cytochrome P450 or 2002;99:11890-5.
aldehyde dehydrogenase isoforms exist and cooperate 3. Saad F, Fizazi K. Androgen deprivation therapy and secondary
hormone therapy in the management of hormone-sensitive and
in retinoic acid production, stem cell maintenance castration-resistant prostate cancer. Urology 2015;86:852-61.
or in inflammatory response may also help to 4. Huggins C, Stevens RE, Hodges CV. Studies on prostatic cancer. II.
understand significant differences between localised The effects of castration on advanced carcinoma of the prostate gland.
and metastasised PCa. As osteoblasts regulate Arch Surg 1941;43:209.
the intratumoral steroidogenesis of CRPC in bone, 5. James ND, Spears MR, Clarke NW, Dearnaley DP, De Bono JS,
targeting osteoblasts may therefore be important in the Gale J, Hetherington J, Hoskin PJ, Jones RJ, Laing R, Lester JF,
development of new therapeutic approaches [175] . To McLaren D, Parker CC, Parmar MK, Ritchie AW, Russell JM, Strebel
RT, Thalmann GN, Mason MD, Sydes MR. Survival with newly
improve on our strategies for therapeutic intervention, diagnosed metastatic prostate cancer in the “docetaxel era”: data from
we need better models for evaluating new compounds, 917 patients in the control arm of the STAMPEDE trial (MRC PR08,
including co-culture systems, multicellular spheroids, CRUK/06/019). Eur Urol 2015;67:1028-38.
patient-derived xenografts and organoids. Discovery 6. Imamura Y, Sadar MD. Androgen receptor targeted therapies in
of highly selective chemical probes to investigate castration-resistant prostate cancer: bench to clinic. Int J Urol
steroidogenic/metabolic pathways should yield new 2016;23:654-65.
drugs that more effectively target the AR axis, which 7. Seisen T, Roupret M, Gomez F, Malouf GG, Shariat SF, Peyronnet
B, Spano JP, Cancel-Tassin G, Cussenot O. A comprehensive review
can be employed in combination with other drugs of genomic landscape, biomarkers and treatment sequencing in
employed in PCa management. castration-resistant prostate cancer. Cancer Treat Rev 2016;48:25-33.
8. Kumagai J, Hofland J, Erkens-Schulze S, Dits NF, Steenbergen J,
DECLARATIONS Jenster G, Homma Y, de Jong FH, van Weerden WM. Intratumoral
conversion of adrenal androgen precursors drives androgen receptor-
activated cell growth in prostate cancer more potently than de novo
Acknowledgments steroidogenesis. Prostate 2013;73:1636-50.
We thank Dr. Davide Bonanni for production of 9. Penning TM. Mechanisms of drug resistance that target the androgen
the crystallographic images, Prof. Franca Viola for axis in castration resistant prostate cancer (CRPC). J Steroid Biochem
helpful discussions and revision of the manuscript Mol Biol 2015;153:105-13.
and Dr. Robert A. Falconer for proofreading the final 10. Sakai M, Martinez-Arguelles DB, Aprikian AG, Magliocco AM,
manuscript. Papadopoulos V. De novo steroid biosynthesis in human prostate cell
lines and biopsies. Prostate 2016;76:575-87.
11. Titus MA, Schell MJ, Lih FB, Tomer KB, Mohler JL. Testosterone
Authors’ contributions and dihydrotestosterone tissue levels in recurrent prostate cancer. Clin
Literature search: A.C. Pippione, D. Boschi Cancer Res 2005;11:4653-7.
Drafting and writing the manuscript: A.C. Pippione, D. 12. Zhang W, Meng Y, Liu N, Wen XF, Yang T. Insights into
Boschi, S. Oliaro-Bosso chemoresistance of prostate cancer. Int J Biol Sci 2015;11:1160-70.
Manuscript’s revision and supervised: K. Pors, S. 13. Cai C, Balk SP. Intratumoral androgen biosynthesis in prostate
Oliaro-Bosso, M.L. Lolli cancer pathogenesis and response to therapy. Endocr Relat Cancer
2011;18:R175-82.
14. Fankhauser M, Tan Y, Hong MKH, Nguyen A, Macintyre G, Haviv
Financial support and sponsorship I, Pedersen JS, Costello AJ, Hovens CM, Corcoran NM. Canonical
Authors acknowledge support in part from University androstenedione reduction is the predominant source of signaling
of Turin (Ricerca Locale grant 2014 and 2015). androgens in hormone-refractory prostate cancer. Clin Cancer Res

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