Bipolar Androgen Therapy in the management of prostate cancer
DOI:
https://doi.org/10.12775/JEHS.2021.11.09.062Keywords
Bipolar Androgen Therapy, prostate cancerAbstract
Introduction and purpose: Prostate cancer (PCa) as one of the most frequent neoplasms in men remains a challenge for oncologists. The main strategy of its treatment is the Androgen Deprivation Therapy (ADT) the principle of which is an inducement of hypogonadism. The lack of testosterone is not only a factor greatly contributing to a decrease of quality of life overall, but additionally it increases the odds of the complications, including low libido and erectile disfunction, metabolic abnormalities, high cardiovascular risk, osteoporosis, anaemia, or depression. ADT also has the potential of inducement of castration resistance (CRPC), which significantly worsen patients prognosis. The main purpose of this review is to explore the Bipolar Androgen Therapy (BAT), which has the potential to solve the aforementioned problems.
State of knowledge: The mechanism of BAT action has been described. BAT is effective not only against CRPC, but androgen-dependant PCa as well. BAT reverses the hormone resistance in CRPC, thus allowing the rechallenging of the ADT. It has the direct cytotoxic effect on cancer cells. Additionally BTA increases the exponents of the general quality of life of the patients. There is a number of active clinical trials regarding BAT.
Conclusions: BAT is a safe therapeutic strategy with the high efficacy in reversing hormone resistance in CRPC patients, thus significantly increasing their health prognoses and it allows to alleviate or avoid the adverse effects of ADT.
References
Kirby M, Hirst C, Crawford ED. Characterising the castration-resistant prostate cancer population: a systematic review. Int J Clin Pract. 2011 Nov;65(11):1180–92.
Weiner AB, Nettey OS, Morgans AK. Management of Metastatic Hormone-Sensitive Prostate Cancer (mHSPC): an Evolving Treatment Paradigm. Curr Treat Options Oncol. 2019 Jul 9;20(9):69.
Gamat M, McNeel DG. Androgen deprivation and immunotherapy for the treatment of prostate cancer. Endocr Relat Cancer. 2017 Dec;24(12):T297–310.
Hotte SJ, Saad F. Current Management of Castrate-Resistant Prostate Cancer. Current Oncology. 2010 Sep;17(s2):72–9.
Rodriguez KM, Pastuszak AW, Khera M. The Role of Testosterone Therapy in the Setting of Prostate Cancer. Curr Urol Rep. 2018 Jun 30;19(8):67.
Huggins C, Hodges CV. Studies on prostatic cancer. I. The effect of castration, of estrogen and of androgen injection on serum phosphatases in metastatic carcinoma of the prostate. 1941. J Urol. 2002 Feb;167(2 Pt 2):948–51; discussion 952.
Prout GR, Brewer WR. Response of men with advanced prostatic carcinoma to exogenous administration of testosterone. Cancer. 1967 Nov;20(11):1871–8.
Fowler JE, Whitmore WF. The response of metastatic adenocarcinoma of the prostate to exogenous testosterone. J Urol. 1981 Sep;126(3):372–5.
Mottet N, van den Bergh RCN, Briers E, Van den Broeck T, Cumberbatch MG, De Santis M, et al. EAU-EANM-ESTRO-ESUR-SIOG Guidelines on Prostate Cancer-2020 Update. Part 1: Screening, Diagnosis, and Local Treatment with Curative Intent. Eur Urol. 2021 Feb;79(2):243–62.
Yamamoto S, Yonese J, Kawakami S, Ohkubo Y, Tatokoro M, Komai Y, et al. Preoperative serum testosterone level as an independent predictor of treatment failure following radical prostatectomy. Eur Urol. 2007 Sep;52(3):696–701.
Imamoto T, Suzuki H, Akakura K, Komiya A, Nakamachi H, Ichikawa T, et al. Pretreatment Serum Level of Testosterone as a Prognostic Factor in Japanese Men with Hormonally Treated Stage D2 Prostate Cancer. Endocrine Journal. 2001;48(5):573–8.
Platz EA, Leitzmann MF, Rifai N, Kantoff PW, Chen Y-C, Stampfer MJ, et al. Sex Steroid Hormones and the Androgen Receptor Gene CAG Repeat and Subsequent Risk of Prostate Cancer in the Prostate-Specific Antigen Era. Cancer Epidemiol Biomarkers Prev. 2005;9.
Wallis CJD, Lo K, Lee Y, Krakowsky Y, Garbens A, Satkunasivam R, et al. Survival and cardiovascular events in men treated with testosterone replacement therapy: an intention-to-treat observational cohort study. Lancet Diabetes Endocrinol. 2016 Jun;4(6):498–506.
Debruyne FMJ, Behre HM, Roehrborn CG, Maggi M, Wu FCW, Schröder FH, et al. Testosterone treatment is not associated with increased risk of prostate cancer or worsening of lower urinary tract symptoms: prostate health outcomes in the Registry of Hypogonadism in Men. BJU Int. 2017 Feb;119(2):216–24.
Robinson D, Van Allen EM, Wu Y-M, Schultz N, Lonigro RJ, Mosquera J-M, et al. Integrative Clinical Genomics of Advanced Prostate Cancer. Cell. 2015 May 21;161(5):1215–28.
Denmeade SR, Isaacs JT. Bipolar androgen therapy: The rationale for rapid cycling of supraphysiologic androgen/ablation in men with castration resistant prostate cancer. The Prostate. 2010;70(14):1600–7.
Tsihlias J, Zhang W, Bhattacharya N, Flanagan M, Klotz L, Slingerland J. Involvement of p27Kip1 in G1 arrest by high dose 5α-dihydrotestosterone in LNCaP human prostate cancer cells. Oncogene. 2000 Feb;19(5):670–9.
Lu L, Schulz H, Wolf DA. The F-box protein SKP2 mediates androgen control of p27 stability in LNCaP human prostate cancer cells. BMC Cell Biology. 2002 Aug 20;3(1):22.
Lu S, Jenster G, Epner DE. Androgen Induction of Cyclin-Dependent Kinase Inhibitor p21 Gene: Role of Androgen Receptor and Transcription Factor Sp1 Complex. Molecular Endocrinology. 2000 May 1;14(5):753–60.
Berchem GJ, Bosseler M, Sugars LY, Voeller HJ, Zeitlin S, Gelmann EP. Androgens induce resistance to bcl-2-mediated apoptosis in LNCaP prostate cancer cells. Cancer Res. 1995 Feb 15;55(4):735–8.
Lin Y, Kokontis J, Tang F, Godfrey B, Liao S, Lin A, et al. Androgen and Its Receptor Promote Bax-Mediated Apoptosis. Molecular and Cellular Biology. 2006 Mar 1;26(5):1908–16.
Litvinov IV, Griend DJV, Antony L, Dalrymple S, Marzo AMD, Drake CG, et al. Androgen receptor as a licensing factor for DNA replication in androgen-sensitive prostate cancer cells. PNAS. 2006 Oct 10;103(41):15085–90.
Cai C, He HH, Chen S, Coleman I, Wang H, Fang Z, et al. Androgen Receptor Gene Expression in Prostate Cancer Is Directly Suppressed by the Androgen Receptor Through Recruitment of Lysine-Specific Demethylase 1. Cancer Cell. 2011 Oct 18;20(4):457–71.
Teply BA, Kachhap S, Eisenberger MA, Denmeade SR. Extreme Response to High-dose Testosterone in BRCA2- and ATM-mutated Prostate Cancer. European Urology. 2017 Mar 1;71(3):499.
Schweizer MT, Antonarakis ES, Wang H, Ajiboye AS, Spitz A, Cao H, et al. Effect of bipolar androgen therapy for asymptomatic men with castration-resistant prostate cancer: results from a pilot clinical study. Sci Transl Med. 2015 Jan 7;7(269):269ra2.
Sena LA, Wang H, Lim ScM SJ, Rifkind I, Ngomba N, Isaacs JT, et al. Bipolar androgen therapy sensitizes castration-resistant prostate cancer to subsequent androgen receptor ablative therapy. Eur J Cancer. 2021 Feb;144:302–9.
Markowski MC, Wang H, Sullivan R, Rifkind I, Sinibaldi V, Schweizer MT, et al. A Multicohort Open-label Phase II Trial of Bipolar Androgen Therapy in Men with Metastatic Castration-resistant Prostate Cancer (RESTORE): A Comparison of Post-abiraterone Versus Post-enzalutamide Cohorts. Eur Urol. 2021 May;79(5):692–9.
Marshall CH, Tunacao J, Danda V, Tsai H-L, Barber J, Gawande R, et al. Reversing the effects of androgen-deprivation therapy in men with metastatic castration-resistant prostate cancer. BJU International. 2021;128(3):366–73.
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