Skip to main content
Erschienen in: Medical Oncology 3/2012

01.09.2012 | Review Article

Old issues and new perspectives on prostate cancer hormonal therapy: the molecular substratum

verfasst von: Leonardo Oliveira Reis

Erschienen in: Medical Oncology | Ausgabe 3/2012

Einloggen, um Zugang zu erhalten

Abstract

Secondary hormonal therapy is a treatment option in patients with castration-resistant prostate cancer (CRPC); however, it is underutilized and is room for optimization and improvement. In this context, androgen receptor (AR) is the Achilles’ heel, being critically important and various mechanisms ranging from receptor mutations to secondary signaling pathways are responsible for some of the biological heterogeneity, demanding a multimodal approach. A comprehensive review of the peer-reviewed literature is performed on the topic of molecular mechanisms supporting secondary hormonal therapies, including expanded alternative hormonal therapies for CRPC. Essential concepts in clinical treatment of patients with progression on primary hormonal therapy are maintaining the castrate state, accounting for the intermittency phenomenon and sequentially using oral antiandrogens and adrenolytics heading to androgen depletion microenvironment. Survival prolongation, pain relief or measurable improvement in tumor-related symptoms should be persecuted and are considered to be a tangible benefit of obvious worth to the patient. Understanding the underlying molecular substratum is of paramount importance to hormonal therapy optimization in this context once current androgen-depletion strategies are incomplete, and residual androgens as well as alternative routes contribute to sustained AR activity and disease progression to a lethal phenotype. One or many mechanisms may be playing a role, even within the same patient and lastly are potential targets for treatment. Five fundamental mechanisms mediated through the AR to promote tumor growth (three of which depend on ligand signaling) added to the stem cell pathway must be recognized in CRPC. They are persistence of intratumoral androgens as a result of in situ steroidogenesis or adrenal source; AR mutations that allow promiscuous activation by otherwise nonsignaling ligands; wild-type AR gene amplification; alterations in AR coactivator-to-corepressor ratio that impact transcription; outlaw AR pathways that bypass the need for androgens by signaling through crosstalk with other ligand-bound receptors, cytokines, or transactivation of activated tyrosine kinase receptors in the cytosol.
Literatur
1.
Zurück zum Zitat Huggins C, Hodges CV. Studies of prostate cancer I. The effect of castration, of oestrogen and of androgen injection on serum phosphatases in metastatic carcinoma f the prostate. Cancer Res. 1941;1:293–301. Huggins C, Hodges CV. Studies of prostate cancer I. The effect of castration, of oestrogen and of androgen injection on serum phosphatases in metastatic carcinoma f the prostate. Cancer Res. 1941;1:293–301.
2.
Zurück zum Zitat Scher HI, Steineck G, Kelly WK. Hormone-refractory (D3) prostate cancer: refining the concept. Urology. 1995;46:142–8.PubMedCrossRef Scher HI, Steineck G, Kelly WK. Hormone-refractory (D3) prostate cancer: refining the concept. Urology. 1995;46:142–8.PubMedCrossRef
3.
Zurück zum Zitat Petrylak DP, Tangen CM, Hussain MHA, et al. Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N Engl J Med. 2004;351:1513–20.PubMedCrossRef Petrylak DP, Tangen CM, Hussain MHA, et al. Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N Engl J Med. 2004;351:1513–20.PubMedCrossRef
4.
Zurück zum Zitat Tannock IF, de Wit R, Berry WR, et al. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med. 2004;351:1502–12.PubMedCrossRef Tannock IF, de Wit R, Berry WR, et al. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med. 2004;351:1502–12.PubMedCrossRef
5.
Zurück zum Zitat Fleming MT, Morris MJ, Heller G, et al. Post-therapy changes in PSA as an outcome measure in prostate cancer clinical trials. Nat Clin Pract Oncol. 2006;3:658–67.PubMedCrossRef Fleming MT, Morris MJ, Heller G, et al. Post-therapy changes in PSA as an outcome measure in prostate cancer clinical trials. Nat Clin Pract Oncol. 2006;3:658–67.PubMedCrossRef
6.
Zurück zum Zitat Scher HI, Halabi S, Tannock I, Morris M, Sternberg CN, Carducci MA, et al. Design and end points of clinical trials for patients with progressive prostate cancer and castrate levels of testosterone: recommendations of the Prostate Cancer Clinical Trials Working Group. J Clin Oncol. 2008;26:1148–59.PubMedCrossRef Scher HI, Halabi S, Tannock I, Morris M, Sternberg CN, Carducci MA, et al. Design and end points of clinical trials for patients with progressive prostate cancer and castrate levels of testosterone: recommendations of the Prostate Cancer Clinical Trials Working Group. J Clin Oncol. 2008;26:1148–59.PubMedCrossRef
7.
Zurück zum Zitat Reis LO, Sasse AD, Matheus WE, Denardi F, Stopiglia RM, da Silva MM, Ferreira U. Prostate cancer: evidence based clinical practice. Actas Urol Esp. 2009;33:344–50.PubMed Reis LO, Sasse AD, Matheus WE, Denardi F, Stopiglia RM, da Silva MM, Ferreira U. Prostate cancer: evidence based clinical practice. Actas Urol Esp. 2009;33:344–50.PubMed
8.
Zurück zum Zitat Claessens F, Denayer S, Van Tilborgh N, Kerkhofs S, Helsen C, Haelens A. Diverse roles of androgen receptor (AR) domains in AR-mediated signaling. Nucl Recept Signal. 2008;6:e008.PubMed Claessens F, Denayer S, Van Tilborgh N, Kerkhofs S, Helsen C, Haelens A. Diverse roles of androgen receptor (AR) domains in AR-mediated signaling. Nucl Recept Signal. 2008;6:e008.PubMed
9.
Zurück zum Zitat Denmeade SR, Lin XS, Isaacs JT. Role of programmed (apoptotic) cell death during the progression and therapy for prostate cancer. Prostate. 1996;28:251–65.PubMedCrossRef Denmeade SR, Lin XS, Isaacs JT. Role of programmed (apoptotic) cell death during the progression and therapy for prostate cancer. Prostate. 1996;28:251–65.PubMedCrossRef
10.
Zurück zum Zitat Chmelar R, Buchanan G, Need EF, et al. Androgen receptor coregulators and their involvement in the development and progression of prostate cancer. Int J Cancer. 2007;120:719–33.PubMedCrossRef Chmelar R, Buchanan G, Need EF, et al. Androgen receptor coregulators and their involvement in the development and progression of prostate cancer. Int J Cancer. 2007;120:719–33.PubMedCrossRef
11.
Zurück zum Zitat Hsieh AC, Small EJ, Ryan CJ. Androgen-response elements in hormone refractory prostate cancer: implications for treatment development. Lancet Oncol. 2007;8:933–9.PubMedCrossRef Hsieh AC, Small EJ, Ryan CJ. Androgen-response elements in hormone refractory prostate cancer: implications for treatment development. Lancet Oncol. 2007;8:933–9.PubMedCrossRef
12.
Zurück zum Zitat Hellerstedt B. Hormonal therapy options for patients with a rising prostate specific antigen level after primary treatment for prostate cancer. Urology. 2003;62:79–86.PubMedCrossRef Hellerstedt B. Hormonal therapy options for patients with a rising prostate specific antigen level after primary treatment for prostate cancer. Urology. 2003;62:79–86.PubMedCrossRef
13.
Zurück zum Zitat Culig Z, Stober J, Gast A, et al. Activation of two mutant androgen receptors from human prostatic carcinoma by adrenal androgens and metabolic derivatives of testosterone. Cancer Detect Prev. 1996;20:68–75.PubMed Culig Z, Stober J, Gast A, et al. Activation of two mutant androgen receptors from human prostatic carcinoma by adrenal androgens and metabolic derivatives of testosterone. Cancer Detect Prev. 1996;20:68–75.PubMed
14.
Zurück zum Zitat Tan J, Sharief Y, Hamil KG, et al. Dehydroepiandrosterone activates mutant androgen receptors expressed in the androgen-dependent human prostate cancer xenograft CWR22 and LNCaP cells. Mol Endocrinol. 1997;11:450–9.PubMedCrossRef Tan J, Sharief Y, Hamil KG, et al. Dehydroepiandrosterone activates mutant androgen receptors expressed in the androgen-dependent human prostate cancer xenograft CWR22 and LNCaP cells. Mol Endocrinol. 1997;11:450–9.PubMedCrossRef
15.
Zurück zum Zitat Serrate C, Loriot Y, De La Motte Rouge T, et al. Diethylstilbestrol (DES) retains activity, is a reasonable option in patients previously treated with docetaxel for castration-resistant prostate cancer. Ann Oncol. 2009;20:965.PubMedCrossRef Serrate C, Loriot Y, De La Motte Rouge T, et al. Diethylstilbestrol (DES) retains activity, is a reasonable option in patients previously treated with docetaxel for castration-resistant prostate cancer. Ann Oncol. 2009;20:965.PubMedCrossRef
16.
Zurück zum Zitat Cleffi S, Neto AS, Reis LO, Maia P, Fonseca F, Wroclawski ML, Neves M, Pompeo AC, Del Giglio A, Faria EF, Tobias-Machado M. Androgen deprivation therapy and morbid obesity: do they share cardiovascular risk through metabolic syndrome? Actas Urol Esp. 2011;35(5):259–65.PubMedCrossRef Cleffi S, Neto AS, Reis LO, Maia P, Fonseca F, Wroclawski ML, Neves M, Pompeo AC, Del Giglio A, Faria EF, Tobias-Machado M. Androgen deprivation therapy and morbid obesity: do they share cardiovascular risk through metabolic syndrome? Actas Urol Esp. 2011;35(5):259–65.PubMedCrossRef
17.
Zurück zum Zitat Mellado B, Codony J, Ribal MJ, Visa L, Gascon P. Molecular biology of androgen-independent prostate cancer: the role of the androgen receptor pathway. Clin Trans Oncol. 2009;11:5–10.CrossRef Mellado B, Codony J, Ribal MJ, Visa L, Gascon P. Molecular biology of androgen-independent prostate cancer: the role of the androgen receptor pathway. Clin Trans Oncol. 2009;11:5–10.CrossRef
18.
Zurück zum Zitat Freeman MR, Cinar B, Lu ML. Membrane rafts as potential sites of nongenomic hormonal signaling in prostate cancer. Trends Endocrinol Metab. 2005;16:273–9.PubMedCrossRef Freeman MR, Cinar B, Lu ML. Membrane rafts as potential sites of nongenomic hormonal signaling in prostate cancer. Trends Endocrinol Metab. 2005;16:273–9.PubMedCrossRef
19.
Zurück zum Zitat Scher HI, Sawyers CL. Biology of progressive, castration-resistant prostate cancer: directed therapies targeting the androgen-receptor signaling axis. J Clin Oncol. 2005;23:8253–61.PubMedCrossRef Scher HI, Sawyers CL. Biology of progressive, castration-resistant prostate cancer: directed therapies targeting the androgen-receptor signaling axis. J Clin Oncol. 2005;23:8253–61.PubMedCrossRef
20.
Zurück zum Zitat Eder IE, Culig Z, Putz T, Nessler-Menardi C, Bartsch G, Klocker H. Molecular biology of the androgen receptor: from molecular understanding to the clinic. Eur Urol. 2001;40:241–51.PubMedCrossRef Eder IE, Culig Z, Putz T, Nessler-Menardi C, Bartsch G, Klocker H. Molecular biology of the androgen receptor: from molecular understanding to the clinic. Eur Urol. 2001;40:241–51.PubMedCrossRef
21.
Zurück zum Zitat Feldman BJ, Feldman D. The development of androgen-independent prostate cancer. Nat Rev Cancer. 2001;1:34–45.PubMedCrossRef Feldman BJ, Feldman D. The development of androgen-independent prostate cancer. Nat Rev Cancer. 2001;1:34–45.PubMedCrossRef
22.
Zurück zum Zitat Buchanan G, Yang M, Cheong A, Harris JM, Irvine RA, Lambert PF, et al. Structural and functional consequences of glutamine tract variation in the androgen receptor. Hum Mol Genet. 2004;13:1677–92.PubMedCrossRef Buchanan G, Yang M, Cheong A, Harris JM, Irvine RA, Lambert PF, et al. Structural and functional consequences of glutamine tract variation in the androgen receptor. Hum Mol Genet. 2004;13:1677–92.PubMedCrossRef
23.
Zurück zum Zitat Veldscholte J, Risstalpers C, Kuiper G, Jenster G, Berrevoets C, Claassen E, et al. A mutation in the ligand-binding domain of the androgen receptor of human Lncap cells affects steroid binding characteristics and response to anti-androgens. Biochem Biophys Res Commu. 1990;173:534–40.CrossRef Veldscholte J, Risstalpers C, Kuiper G, Jenster G, Berrevoets C, Claassen E, et al. A mutation in the ligand-binding domain of the androgen receptor of human Lncap cells affects steroid binding characteristics and response to anti-androgens. Biochem Biophys Res Commu. 1990;173:534–40.CrossRef
24.
Zurück zum Zitat Taplin ME, Bubley GJ, Shuster TD, et al. Mutations of the androgen-receptor gene in metastatic androgen independent prostate cancer. N Engl J Med. 1995;332:1393–8.PubMedCrossRef Taplin ME, Bubley GJ, Shuster TD, et al. Mutations of the androgen-receptor gene in metastatic androgen independent prostate cancer. N Engl J Med. 1995;332:1393–8.PubMedCrossRef
25.
Zurück zum Zitat Dehm SM, Schmidt LJ, Heemers HV, et al. Splicing of a novel androgen receptor exon generates a constitutively active androgen receptor that mediates prostate cancer therapy resistance. Cancer Res. 2008;68:5469–77.PubMedCrossRef Dehm SM, Schmidt LJ, Heemers HV, et al. Splicing of a novel androgen receptor exon generates a constitutively active androgen receptor that mediates prostate cancer therapy resistance. Cancer Res. 2008;68:5469–77.PubMedCrossRef
26.
Zurück zum Zitat Chen CD, Welsbie DS, Tran C, Baek SH, Chen R, Vessella R, et al. Molecular determinants of resistance to antiandrogen therapy. Nat Med. 2004;10:33–9.PubMedCrossRef Chen CD, Welsbie DS, Tran C, Baek SH, Chen R, Vessella R, et al. Molecular determinants of resistance to antiandrogen therapy. Nat Med. 2004;10:33–9.PubMedCrossRef
27.
Zurück zum Zitat Dehm SM, Tindall DJ. Androgen receptor structural and functional elements: role and regulation in prostate cancer. Mol Endocrinol. 2007;21:2855–63.PubMedCrossRef Dehm SM, Tindall DJ. Androgen receptor structural and functional elements: role and regulation in prostate cancer. Mol Endocrinol. 2007;21:2855–63.PubMedCrossRef
28.
Zurück zum Zitat Holzbeierlein J, Lal P, LaTulippe E, et al. Gene expression analysis of human prostate carcinoma during hormonal therapy identifies androgen-responsive genes and mechanisms of therapy resistance. Am J Pathol. 2004;164:217–27.PubMedCrossRef Holzbeierlein J, Lal P, LaTulippe E, et al. Gene expression analysis of human prostate carcinoma during hormonal therapy identifies androgen-responsive genes and mechanisms of therapy resistance. Am J Pathol. 2004;164:217–27.PubMedCrossRef
29.
Zurück zum Zitat Cohen BL, Gomez P, Omori Y, Duncan RC, Civantos F, Soloway MS, Lokeshwar VB, Lokeshwar BL. Cyclooxygenase-2 (cox-2) expression is an independent predictor of prostate cancer recurrence. Int J Cancer. 2006;119:1082–7.PubMedCrossRef Cohen BL, Gomez P, Omori Y, Duncan RC, Civantos F, Soloway MS, Lokeshwar VB, Lokeshwar BL. Cyclooxygenase-2 (cox-2) expression is an independent predictor of prostate cancer recurrence. Int J Cancer. 2006;119:1082–7.PubMedCrossRef
30.
Zurück zum Zitat Quinn DI, Henshall SM, Sutherland RL. Molecular markers of prostate cancer outcome. Eur J Cancer. 2005;41:858–87.PubMedCrossRef Quinn DI, Henshall SM, Sutherland RL. Molecular markers of prostate cancer outcome. Eur J Cancer. 2005;41:858–87.PubMedCrossRef
31.
Zurück zum Zitat Need EF, Scher HI, Peters AA, Moore NL, Cheong A, Ryan CJ, et al. A Novel androgen receptor amino terminal region reveals two classes of amino/carboxyl interaction-deficient variants with divergent capacity to activate responsive sites in chromatin. Endocrinology. 2009;150:2674–82.PubMedCrossRef Need EF, Scher HI, Peters AA, Moore NL, Cheong A, Ryan CJ, et al. A Novel androgen receptor amino terminal region reveals two classes of amino/carboxyl interaction-deficient variants with divergent capacity to activate responsive sites in chromatin. Endocrinology. 2009;150:2674–82.PubMedCrossRef
32.
Zurück zum Zitat Chen CD, Welsbie DS, Tran C, Baek SH, Chen R, Vessella R, Rosenfeld MG, Sawyers CL. Molecular determinants of resistance to anti-androgen therapy. Nature Med. 2004;10:33–9.PubMedCrossRef Chen CD, Welsbie DS, Tran C, Baek SH, Chen R, Vessella R, Rosenfeld MG, Sawyers CL. Molecular determinants of resistance to anti-androgen therapy. Nature Med. 2004;10:33–9.PubMedCrossRef
33.
Zurück zum Zitat Baron S, Manin M, Beaudoin C, Leotoing L, Communal Y, Veyssiere G, et al. Androgen receptor mediates non-genomic activation of phosphatidylinositol 3-oh kinase in androgen-sensitive epithelial cells. J Biol Chem. 2004;279:14579–86.PubMedCrossRef Baron S, Manin M, Beaudoin C, Leotoing L, Communal Y, Veyssiere G, et al. Androgen receptor mediates non-genomic activation of phosphatidylinositol 3-oh kinase in androgen-sensitive epithelial cells. J Biol Chem. 2004;279:14579–86.PubMedCrossRef
34.
Zurück zum Zitat Migliaccio A, Castoria G, Di Domenico M, De Falco A, Bilancio A, Lombardi M, et al. Steroid-induced androgen receptor-oestradiol receptor beta-src complex triggers prostate cancer cell proliferation. EMBO J. 2000;19:5406–17.PubMedCrossRef Migliaccio A, Castoria G, Di Domenico M, De Falco A, Bilancio A, Lombardi M, et al. Steroid-induced androgen receptor-oestradiol receptor beta-src complex triggers prostate cancer cell proliferation. EMBO J. 2000;19:5406–17.PubMedCrossRef
35.
Zurück zum Zitat Peterziel H, Mink S, Schonert A, Becker M, Klocker H, Cato ACB. Rapid signalling by androgen receptor in prostate cancer cells. Oncogene. 1999;18:6322–9.PubMedCrossRef Peterziel H, Mink S, Schonert A, Becker M, Klocker H, Cato ACB. Rapid signalling by androgen receptor in prostate cancer cells. Oncogene. 1999;18:6322–9.PubMedCrossRef
36.
Zurück zum Zitat Malinowska K, Neuwirt H, Cavarretta IT, Bektic J, Steiner H, Dietrich H, et al. Interleukin-6 stimulation of growth of prostate cancer in vitro and in vivo through activation of the androgen receptor. Endocr Relat Cancer. 2009;16:155–69.PubMedCrossRef Malinowska K, Neuwirt H, Cavarretta IT, Bektic J, Steiner H, Dietrich H, et al. Interleukin-6 stimulation of growth of prostate cancer in vitro and in vivo through activation of the androgen receptor. Endocr Relat Cancer. 2009;16:155–69.PubMedCrossRef
37.
Zurück zum Zitat Robinson DR, Zylstra CR, Williams BO. Wnt signaling and prostate cancer. Curr Drug Targets. 2008;9:571–80.PubMedCrossRef Robinson DR, Zylstra CR, Williams BO. Wnt signaling and prostate cancer. Curr Drug Targets. 2008;9:571–80.PubMedCrossRef
38.
Zurück zum Zitat Seaton A, Scullin P, Maxwell PJ, Wilson C, Pettigrew J, Gallagher R, et al. Interleukin-8 signaling promotes androgen-independent proliferation of prostate cancer cells via induction of androgen receptor expression and activation. Carcinogenesis. 2008;29:1148–56.PubMedCrossRef Seaton A, Scullin P, Maxwell PJ, Wilson C, Pettigrew J, Gallagher R, et al. Interleukin-8 signaling promotes androgen-independent proliferation of prostate cancer cells via induction of androgen receptor expression and activation. Carcinogenesis. 2008;29:1148–56.PubMedCrossRef
39.
Zurück zum Zitat Dagvadorj A, Collins S, Jomain JB, Abdulghani J, Karras J, Zellweger T, Li H, Nurmi M, Alanen K, Mirtti T, Visakorpi T, Bubendorf L, Goffin V, Nevalainen MT. Autocrine prolactin promotes prostate cancer cell growth via Janus kinase-2-signal transducer and activator of transcription-5a/b signaling pathway. Endocrinology. 2007;148:3089–101.PubMedCrossRef Dagvadorj A, Collins S, Jomain JB, Abdulghani J, Karras J, Zellweger T, Li H, Nurmi M, Alanen K, Mirtti T, Visakorpi T, Bubendorf L, Goffin V, Nevalainen MT. Autocrine prolactin promotes prostate cancer cell growth via Janus kinase-2-signal transducer and activator of transcription-5a/b signaling pathway. Endocrinology. 2007;148:3089–101.PubMedCrossRef
40.
Zurück zum Zitat Montgomery RB, Mostaghel EA, Vessella R, Hess DL, Kalhorn TF, Higano CS, True LD, Nelson PS. Maintenance of intratumoral androgens in metastatic prostate cancer: a mechanism for castration-resistant tumor growth. Cancer Res. 2008;68:4447–54.PubMedCrossRef Montgomery RB, Mostaghel EA, Vessella R, Hess DL, Kalhorn TF, Higano CS, True LD, Nelson PS. Maintenance of intratumoral androgens in metastatic prostate cancer: a mechanism for castration-resistant tumor growth. Cancer Res. 2008;68:4447–54.PubMedCrossRef
41.
Zurück zum Zitat Geller J, Albert J, Nachtsheim D, Loza D, Lippman S. Steroid levels in cancer of the prostate–markers of tumor differentiation and adequacy of antiandrogen therapy. Prog Clin Biol Res. 1979;33:103–11.PubMed Geller J, Albert J, Nachtsheim D, Loza D, Lippman S. Steroid levels in cancer of the prostate–markers of tumor differentiation and adequacy of antiandrogen therapy. Prog Clin Biol Res. 1979;33:103–11.PubMed
42.
Zurück zum Zitat Geller J, de la Vega DJ, Albert JD, Nachtsheim DA. Tissue dihydrotestosterone levels and clinical response to hormonal therapy in patients with advanced prostate cancer. J Clin Endocrinol Metab. 1984;58:36–40.PubMedCrossRef Geller J, de la Vega DJ, Albert JD, Nachtsheim DA. Tissue dihydrotestosterone levels and clinical response to hormonal therapy in patients with advanced prostate cancer. J Clin Endocrinol Metab. 1984;58:36–40.PubMedCrossRef
43.
Zurück zum Zitat Mohler JL, Gregory CW, Ford OH 3rd, Kim D, Weaver CM, Petrusz P, Wilson EM, French FS. The androgen axis in recurrent prostate cancer. Clin Cancer Res. 2004;10:440–8.PubMedCrossRef Mohler JL, Gregory CW, Ford OH 3rd, Kim D, Weaver CM, Petrusz P, Wilson EM, French FS. The androgen axis in recurrent prostate cancer. Clin Cancer Res. 2004;10:440–8.PubMedCrossRef
44.
Zurück zum Zitat Mostaghel EA, Page ST, Lin DW, Fazli L, Coleman IM, True LD, Knudsen B, Hess DL, Nelson CC, Matsumoto AM, 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.PubMedCrossRef Mostaghel EA, Page ST, Lin DW, Fazli L, Coleman IM, True LD, Knudsen B, Hess DL, Nelson CC, Matsumoto AM, 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.PubMedCrossRef
45.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
46.
Zurück zum Zitat Labrie F, Belanger A, Dupont A, Luu-The V, Simard J, Labrie C. Science behind total androgen blockade: from gene to combination therapy. Clin Invest Med. 1993;16:475–92.PubMed Labrie F, Belanger A, Dupont A, Luu-The V, Simard J, Labrie C. Science behind total androgen blockade: from gene to combination therapy. Clin Invest Med. 1993;16:475–92.PubMed
47.
Zurück zum Zitat Palapattu GS, Wu C, Silvers CR, Martin HB, Williams K, Salamone L, Bushnell T, Huang LS, Yang Q, Huang J. Selective expression of CD44, a putative prostate cancer stem cell marker, in neuroendocrine tumor cells of human prostate cancer. Prostate. 2009;69:787–98.PubMedCrossRef Palapattu GS, Wu C, Silvers CR, Martin HB, Williams K, Salamone L, Bushnell T, Huang LS, Yang Q, Huang J. Selective expression of CD44, a putative prostate cancer stem cell marker, in neuroendocrine tumor cells of human prostate cancer. Prostate. 2009;69:787–98.PubMedCrossRef
48.
Zurück zum Zitat Reis LO, Vieira LF, Zani EL, Denardi F, de Oliveira LC, Ferreira U. Assessment of serum chromogranin-A as prognostic factor in high-risk prostate cancer. J Investig Med. 2010;58:957–60.PubMed Reis LO, Vieira LF, Zani EL, Denardi F, de Oliveira LC, Ferreira U. Assessment of serum chromogranin-A as prognostic factor in high-risk prostate cancer. J Investig Med. 2010;58:957–60.PubMed
49.
Zurück zum Zitat Gugliotta A, Ferreira U, Reis LO, Matheus WE, Denardi F, Mamprim Stopiglia R, Piccolotto Naccarato AM. Satisfaction analysis in men presenting with localized prostate cancer treated with radical prostatectomy or radiotherapy: psychological and social aspects. Actas Urol Esp. 2008;32:411–6.PubMed Gugliotta A, Ferreira U, Reis LO, Matheus WE, Denardi F, Mamprim Stopiglia R, Piccolotto Naccarato AM. Satisfaction analysis in men presenting with localized prostate cancer treated with radical prostatectomy or radiotherapy: psychological and social aspects. Actas Urol Esp. 2008;32:411–6.PubMed
50.
Zurück zum Zitat Andriole GL, Humphrey P, Ray P, et al. Effect of the dual 5alpha-reductase inhibitor dutasteride on markers of tumor regression in prostate cancer. J Urol. 2004;172:915–9.PubMedCrossRef Andriole GL, Humphrey P, Ray P, et al. Effect of the dual 5alpha-reductase inhibitor dutasteride on markers of tumor regression in prostate cancer. J Urol. 2004;172:915–9.PubMedCrossRef
51.
Zurück zum Zitat Reis LO, Pereira TC, Lopes-Cendes I, Ferreira U. MicroRNAs: a new paradigm on molecular urological oncology. Urology. 2010;76:521–7.PubMedCrossRef Reis LO, Pereira TC, Lopes-Cendes I, Ferreira U. MicroRNAs: a new paradigm on molecular urological oncology. Urology. 2010;76:521–7.PubMedCrossRef
Metadaten
Titel
Old issues and new perspectives on prostate cancer hormonal therapy: the molecular substratum
verfasst von
Leonardo Oliveira Reis
Publikationsdatum
01.09.2012
Verlag
Springer US
Erschienen in
Medical Oncology / Ausgabe 3/2012
Print ISSN: 1357-0560
Elektronische ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-011-9991-z

Weitere Artikel der Ausgabe 3/2012

Medical Oncology 3/2012 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.