Document Type : Review Article
Authors
1 Department of Community Medicine, Hawler Medical University, Erbil, Iraq.
2 Department of molecular genetics, Ahar Branch, Islamic Azad university, Ahar, Iran
Abstract
Prostate cancer represents a major health problem in men worldwide. Androgens are required for the growth and maintenance of the prostate. The androgen-signaling axis plays a pivotal role in the pathogenesis of prostate cancer. Clinical treatments that target steroidogenesis and the androgen receptor (AR) successfully postpone disease progression. The role of androgens and AR signaling has been well characterized in metastatic prostate cancer, where it has been shown that prostate cancer cells are exquisitely adept at maintaining functional AR signaling to drive cancer growth. This review summarizes the current information regarding the role of androgens in prostate cancer.
Keywords
1.Toivanen R, Shen MM. Prostate organogenesis: tissue induction, hormonal regulation and cell type specification. Development. 2017 Apr 15;144(8):1382-98.McNeal JE. Normal and pathologic anatomy of prostate. Urology. 1981;17:11-6.
2.Pernar CH, Ebot EM, Wilson KM, Mucci LA. The epidemiology of prostate cancer. Cold Spring Harbor perspectives in medicine. 2018 Dec 1;8(12):a030361.
3.Tafuri A, Porcaro AB, Shakir A, Migliorini F, Verratti V, Brunelli M, Cerruto MA, Antonelli A. Serum testosterone and obesity in prostate cancer biology: a call for health promotion in the ageing male. Aging Clinical and Experimental Research. 2021 May;33(5):1399-401.
4.H Lajis N, Abas F, Othman I, Naidu R. Mechanism of anti-cancer activity of curcumin on androgen-dependent and androgen-independent prostate cancer. Nutrients. 2020 Mar;12(3):679.
5.Chatterjee P, Schweizer MT, Lucas JM, Coleman I, Nyquist MD, Frank SB, Tharakan R, Mostaghel E, Luo J, Pritchard CC, Lam HM. Supraphysiological androgens suppress prostate cancer growth through androgen receptor–mediated DNA damage. The Journal of clinical investigation. 2019 Oct 1;129(10):4245-60.
6.Fujita K, Nonomura N. Role of androgen receptor in prostate cancer: a review. The world journal of men’s health. 2019 Sep 1;37(3):288-95.
7.Ghashghaei M, Paliouras M, Heravi M, Bekerat H, Trifiro M, Niazi TM, Muanza T. Enhanced radiosensitization of enzalutamide via schedule dependent administration to androgen‐sensitive prostate cancer cells. The Prostate. 2018 Jan;78(1):64-75.
8.Pierorazio PM, Ferrucci L, Kettermann A, Longo DL, Metter EJ, Carter HB. Serum testosterone is associated with aggressive prostate cancer in older men: results from the Baltimore Longitudinal Study of Aging. BJU international. 2010 Mar;105(6):824.
9.Kalra R, Bhagyaraj E, Tiwari D, Nanduri R, Chacko AP, Jain M, Mahajan S, Khatri N, Gupta P. AIRE promotes androgen-independent prostate cancer by directly regulating IL-6 and modulating tumor microenvironment. Oncogenesis. 2018 May 25;7(5):1-5.
10.Zhang C, Li P, Wen Y, Feng G, Liu Y, Zhang Y, Xu Y, Zhang Z. The promotion on cell growth of androgen-dependent prostate cancer by antimony via mimicking androgen activity. Toxicology letters. 2018 May 15;288:136-42.
11.Lombardi AP, Vicente CM, Porto CS. Estrogen receptors promote migration, invasion and colony formation of the androgen-independent prostate cancer cells PC-3 through β-catenin pathway. Frontiers in Endocrinology. 2020 Apr 9;11:184.
12.Berchuck JE, Viscuse PV, Beltran H, Aparicio A. Clinical considerations for the management of androgen indifferent prostate cancer. Prostate cancer and prostatic diseases. 2021 Sep;24(3):623-37.
13.Lamb DJ, Weigel NL, Marcell M. Androgen receptors and their biology.
14.Bakouny Z, Yekedüz E, Braun DA, Berchuck JE, Hirsch L, Utkan G, Lee Y, Trinh QD, Choueiri TK, Ürün Y. Neurotoxicities of novel non-steroidal anti-androgens for prostate cancer: A systematic review and meta-analysis. Critical reviews in oncology/hematology. 2021 Oct 1;166:103463.
15.A.H. Davies, H. Beltran, A. Zoubeidi, Cellular plasticity and the neuroendocrine phenotype in prostate cancer, Nat. Rev. Urol. 15 (2018) 271–286.
16.Hou Z, Huang S, Li Z. Androgens in prostate cancer: A tale that never ends. Cancer Letters. 2021 Sep 28;516:1-2.
17.Bakouny Z, Yekedüz E, Braun DA, Berchuck JE, Hirsch L, Utkan G, Lee Y, Trinh QD, Choueiri TK, Ürün Y. Neurotoxicities of novel non-steroidal anti-androgens for prostate cancer: A systematic review and meta-analysis. Critical reviews in oncology/hematology. 2021 Oct 1;166:103463.
18.Hao L, Dong Y, Zhang JJ, He HG, Chen JG, Zhang SQ, Zhang QJ, Wu W, Han CH, Shi ZD. Melatonin decreases androgen-sensitive prostate cancer growth by suppressing SENP1 expression. Translational Andrology and Urology. 2022 Jan;11(1):91.
19.Castoria G, Lombardi M, Barone MV, Bilancio A, Di Domenico M, Bottero D, Vitale F, Migliaccio A, Auricchio F. Androgen-stimulated DNA synthesis and cytoskeletal changes in fibroblasts by a nontranscriptional receptor action. The Journal of cell biology. 2003 May 12;161(3):547-56.
20.Rao A, Moka N, Hamstra DA, Ryan CJ. Co-Inhibition of Androgen Receptor and PARP as a Novel Treatment Paradigm in Prostate Cancer—Where Are We Now?. Cancers. 2022 Feb 4;14(3):801.
21.Anjaly K, Tiku AB. Caffeic acid phenethyl ester induces radiosensitization via inhibition of DNA damage repair in androgen‐independent prostate cancer cells. Environmental Toxicology. 2022 Jan 10.
22.Scher HI, Fizazi K, Saad F, Taplin ME, Sternberg CN, Miller K, De Wit R, Mulders P, Chi KN, Shore ND, Armstrong AJ. Increased survival with enzalutamide in prostate cancer after chemotherapy. New England Journal of Medicine. 2012 Sep 27;367(13):1187-97.
23.Lu Y, Zhang Z, Yu H, Zheng SL, Isaacs WB, Xu J, Sun J. Functional annotation of risk loci identified through genome‐wide association studies for prostate cancer. The Prostate. 2011 Jun 15;71(9):955-63.
24.Ewing CM, Ray AM, Lange EM, Zuhlke KA, Robbins CM, Tembe WD, Wiley KE, Isaacs SD, Johng D, Wang Y, Bizon C. Germline mutations in HOXB13 and prostate-cancer risk. New England Journal of Medicine. 2012 Jan 12;366(2):141-9.
25.Sharifi N, Auchus RJ. Steroid biosynthesis and prostate cancer. Steroids. 2012 Jun 1;77(7):719-26.
26.Fontana F, Anselmi M, Limonta P. Molecular mechanisms and genetic alterations in prostate cancer: From diagnosis to targeted therapy. Cancer Letters. 2022 Mar 8:215619.
27.Mirzakhani K, Kallenbach J, Rasa SM, Ribaudo F, Ungelenk M, Ehsani M, Gong W, Gassler N, Leeder M, Grimm MO, Neri F. The androgen receptor—lncRNASAT1-AKT-p15 axis mediates androgen-induced cellular senescence in prostate cancer cells. Oncogene. 2022 Feb;41(7):943-59.
28.Suarez-Almazor ME, Pundole X, Cabanillas G, Lei X, Zhao H, Elting LS, Lopez-Olivo MA, Giordano SH. Association of Bone Mineral Density Testing With Risk of Major Osteoporotic Fractures Among Older Men Receiving Androgen Deprivation Therapy to Treat Localized or Regional Prostate Cancer. JAMA network open. 2022 Apr 1;5(4):e225432-.
29.Knudsen KE, Scher HI. Starving the addiction: new opportunities for durable suppression of AR signaling in prostate cancer. Clinical Cancer Research. 2009 Aug 1;15(15):4792-8.
30.Grossmann M, Zajac JD. Management of side effects of androgen deprivation therapy. Endocrinology and Metabolism Clinics. 2011 Sep 1;40(3):655-71.
31.Ryan CJ, Smith MR, De Bono JS, Molina A, Logothetis CJ, De Souza P, Fizazi K, Mainwaring P, Piulats JM, Ng S, Carles J. Abiraterone in metastatic prostate cancer without previous chemotherapy. New England Journal of Medicine. 2013 Jan 10;368(2):138-48.
32.Westaby D, Maza MD, Paschalis A, Jimenez-Vacas JM, Welti J, de Bono J, Sharp A. A new old target: Androgen receptor signaling and advanced prostate cancer. Annual review of pharmacology and toxicology. 2021 Aug 24;62.
33.Spitzer M, Huang G, Basaria S, Travison TG, Bhasin S. Risks and benefits of testosterone therapy in older men. Nature reviews Endocrinology. 2013 Jul;9(7):414-24.
34.Formaggio N, Rubin MA, Theurillat JP. Loss and revival of androgen receptor signaling in advanced prostate cancer. Oncogene. 2021 Feb;40(7):1205-16.
35.Evans AJ. Treatment effects in prostate cancer. Modern Pathology. 2018 Jan;31(1):110-21.
36.Dai C, Heemers H, Sharifi N. Androgen signaling in prostate cancer. Cold Spring Harbor perspectives in medicine. 2017 Sep 1;7(9):a030452.
37.Crawford ED, Heidenreich A, Lawrentschuk N, Tombal B, Pompeo AC, Mendoza-Valdes A, Miller K, Debruyne FM, Klotz L. Androgen-targeted therapy in men with prostate cancer: evolving practice and future considerations. Prostate cancer and prostatic diseases. 2019 Mar;22(1):24-38.
2.Pernar CH, Ebot EM, Wilson KM, Mucci LA. The epidemiology of prostate cancer. Cold Spring Harbor perspectives in medicine. 2018 Dec 1;8(12):a030361.
3.Tafuri A, Porcaro AB, Shakir A, Migliorini F, Verratti V, Brunelli M, Cerruto MA, Antonelli A. Serum testosterone and obesity in prostate cancer biology: a call for health promotion in the ageing male. Aging Clinical and Experimental Research. 2021 May;33(5):1399-401.
4.H Lajis N, Abas F, Othman I, Naidu R. Mechanism of anti-cancer activity of curcumin on androgen-dependent and androgen-independent prostate cancer. Nutrients. 2020 Mar;12(3):679.
5.Chatterjee P, Schweizer MT, Lucas JM, Coleman I, Nyquist MD, Frank SB, Tharakan R, Mostaghel E, Luo J, Pritchard CC, Lam HM. Supraphysiological androgens suppress prostate cancer growth through androgen receptor–mediated DNA damage. The Journal of clinical investigation. 2019 Oct 1;129(10):4245-60.
6.Fujita K, Nonomura N. Role of androgen receptor in prostate cancer: a review. The world journal of men’s health. 2019 Sep 1;37(3):288-95.
7.Ghashghaei M, Paliouras M, Heravi M, Bekerat H, Trifiro M, Niazi TM, Muanza T. Enhanced radiosensitization of enzalutamide via schedule dependent administration to androgen‐sensitive prostate cancer cells. The Prostate. 2018 Jan;78(1):64-75.
8.Pierorazio PM, Ferrucci L, Kettermann A, Longo DL, Metter EJ, Carter HB. Serum testosterone is associated with aggressive prostate cancer in older men: results from the Baltimore Longitudinal Study of Aging. BJU international. 2010 Mar;105(6):824.
9.Kalra R, Bhagyaraj E, Tiwari D, Nanduri R, Chacko AP, Jain M, Mahajan S, Khatri N, Gupta P. AIRE promotes androgen-independent prostate cancer by directly regulating IL-6 and modulating tumor microenvironment. Oncogenesis. 2018 May 25;7(5):1-5.
10.Zhang C, Li P, Wen Y, Feng G, Liu Y, Zhang Y, Xu Y, Zhang Z. The promotion on cell growth of androgen-dependent prostate cancer by antimony via mimicking androgen activity. Toxicology letters. 2018 May 15;288:136-42.
11.Lombardi AP, Vicente CM, Porto CS. Estrogen receptors promote migration, invasion and colony formation of the androgen-independent prostate cancer cells PC-3 through β-catenin pathway. Frontiers in Endocrinology. 2020 Apr 9;11:184.
12.Berchuck JE, Viscuse PV, Beltran H, Aparicio A. Clinical considerations for the management of androgen indifferent prostate cancer. Prostate cancer and prostatic diseases. 2021 Sep;24(3):623-37.
13.Lamb DJ, Weigel NL, Marcell M. Androgen receptors and their biology.
14.Bakouny Z, Yekedüz E, Braun DA, Berchuck JE, Hirsch L, Utkan G, Lee Y, Trinh QD, Choueiri TK, Ürün Y. Neurotoxicities of novel non-steroidal anti-androgens for prostate cancer: A systematic review and meta-analysis. Critical reviews in oncology/hematology. 2021 Oct 1;166:103463.
15.A.H. Davies, H. Beltran, A. Zoubeidi, Cellular plasticity and the neuroendocrine phenotype in prostate cancer, Nat. Rev. Urol. 15 (2018) 271–286.
16.Hou Z, Huang S, Li Z. Androgens in prostate cancer: A tale that never ends. Cancer Letters. 2021 Sep 28;516:1-2.
17.Bakouny Z, Yekedüz E, Braun DA, Berchuck JE, Hirsch L, Utkan G, Lee Y, Trinh QD, Choueiri TK, Ürün Y. Neurotoxicities of novel non-steroidal anti-androgens for prostate cancer: A systematic review and meta-analysis. Critical reviews in oncology/hematology. 2021 Oct 1;166:103463.
18.Hao L, Dong Y, Zhang JJ, He HG, Chen JG, Zhang SQ, Zhang QJ, Wu W, Han CH, Shi ZD. Melatonin decreases androgen-sensitive prostate cancer growth by suppressing SENP1 expression. Translational Andrology and Urology. 2022 Jan;11(1):91.
19.Castoria G, Lombardi M, Barone MV, Bilancio A, Di Domenico M, Bottero D, Vitale F, Migliaccio A, Auricchio F. Androgen-stimulated DNA synthesis and cytoskeletal changes in fibroblasts by a nontranscriptional receptor action. The Journal of cell biology. 2003 May 12;161(3):547-56.
20.Rao A, Moka N, Hamstra DA, Ryan CJ. Co-Inhibition of Androgen Receptor and PARP as a Novel Treatment Paradigm in Prostate Cancer—Where Are We Now?. Cancers. 2022 Feb 4;14(3):801.
21.Anjaly K, Tiku AB. Caffeic acid phenethyl ester induces radiosensitization via inhibition of DNA damage repair in androgen‐independent prostate cancer cells. Environmental Toxicology. 2022 Jan 10.
22.Scher HI, Fizazi K, Saad F, Taplin ME, Sternberg CN, Miller K, De Wit R, Mulders P, Chi KN, Shore ND, Armstrong AJ. Increased survival with enzalutamide in prostate cancer after chemotherapy. New England Journal of Medicine. 2012 Sep 27;367(13):1187-97.
23.Lu Y, Zhang Z, Yu H, Zheng SL, Isaacs WB, Xu J, Sun J. Functional annotation of risk loci identified through genome‐wide association studies for prostate cancer. The Prostate. 2011 Jun 15;71(9):955-63.
24.Ewing CM, Ray AM, Lange EM, Zuhlke KA, Robbins CM, Tembe WD, Wiley KE, Isaacs SD, Johng D, Wang Y, Bizon C. Germline mutations in HOXB13 and prostate-cancer risk. New England Journal of Medicine. 2012 Jan 12;366(2):141-9.
25.Sharifi N, Auchus RJ. Steroid biosynthesis and prostate cancer. Steroids. 2012 Jun 1;77(7):719-26.
26.Fontana F, Anselmi M, Limonta P. Molecular mechanisms and genetic alterations in prostate cancer: From diagnosis to targeted therapy. Cancer Letters. 2022 Mar 8:215619.
27.Mirzakhani K, Kallenbach J, Rasa SM, Ribaudo F, Ungelenk M, Ehsani M, Gong W, Gassler N, Leeder M, Grimm MO, Neri F. The androgen receptor—lncRNASAT1-AKT-p15 axis mediates androgen-induced cellular senescence in prostate cancer cells. Oncogene. 2022 Feb;41(7):943-59.
28.Suarez-Almazor ME, Pundole X, Cabanillas G, Lei X, Zhao H, Elting LS, Lopez-Olivo MA, Giordano SH. Association of Bone Mineral Density Testing With Risk of Major Osteoporotic Fractures Among Older Men Receiving Androgen Deprivation Therapy to Treat Localized or Regional Prostate Cancer. JAMA network open. 2022 Apr 1;5(4):e225432-.
29.Knudsen KE, Scher HI. Starving the addiction: new opportunities for durable suppression of AR signaling in prostate cancer. Clinical Cancer Research. 2009 Aug 1;15(15):4792-8.
30.Grossmann M, Zajac JD. Management of side effects of androgen deprivation therapy. Endocrinology and Metabolism Clinics. 2011 Sep 1;40(3):655-71.
31.Ryan CJ, Smith MR, De Bono JS, Molina A, Logothetis CJ, De Souza P, Fizazi K, Mainwaring P, Piulats JM, Ng S, Carles J. Abiraterone in metastatic prostate cancer without previous chemotherapy. New England Journal of Medicine. 2013 Jan 10;368(2):138-48.
32.Westaby D, Maza MD, Paschalis A, Jimenez-Vacas JM, Welti J, de Bono J, Sharp A. A new old target: Androgen receptor signaling and advanced prostate cancer. Annual review of pharmacology and toxicology. 2021 Aug 24;62.
33.Spitzer M, Huang G, Basaria S, Travison TG, Bhasin S. Risks and benefits of testosterone therapy in older men. Nature reviews Endocrinology. 2013 Jul;9(7):414-24.
34.Formaggio N, Rubin MA, Theurillat JP. Loss and revival of androgen receptor signaling in advanced prostate cancer. Oncogene. 2021 Feb;40(7):1205-16.
35.Evans AJ. Treatment effects in prostate cancer. Modern Pathology. 2018 Jan;31(1):110-21.
36.Dai C, Heemers H, Sharifi N. Androgen signaling in prostate cancer. Cold Spring Harbor perspectives in medicine. 2017 Sep 1;7(9):a030452.
37.Crawford ED, Heidenreich A, Lawrentschuk N, Tombal B, Pompeo AC, Mendoza-Valdes A, Miller K, Debruyne FM, Klotz L. Androgen-targeted therapy in men with prostate cancer: evolving practice and future considerations. Prostate cancer and prostatic diseases. 2019 Mar;22(1):24-38.
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