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Erschienen in: Discover Oncology 3/2016

11.03.2016 | Review

The Metabolism, Analysis, and Targeting of Steroid Hormones in Breast and Prostate Cancer

verfasst von: Cameron P. Capper, James M. Rae, Richard J. Auchus

Erschienen in: Discover Oncology | Ausgabe 3/2016

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Abstract

Breast and prostate cancers are malignancies in which steroid hormones drive cellular proliferation. Over the past century, this understanding has led to successful treatment strategies aimed to inhibit hormone-mediated tumor growth. Nonetheless, disease relapse and progression still pose significant clinical problems, with recurrent and metastatic tumors often exhibiting resistance to current drug therapies. The central role of androgens and estrogens in prostate and breast cancer etiology explains not only why endocrine therapies are often initially successful but also why many tumors ultimately become resistant. It is hypothesized that reducing the concentration of active hormones in the systemic circulation may be insufficient to block cancer progression, as this action selects for tumor cells that can generate active steroids from circulating precursors. This review aims to highlight the currently known differences of steroid biosynthesis in normal physiology versus hormone-dependent cancers, modern approaches to the assessment and targeting of these pathways, and priorities for future research.
Literatur
2.
Zurück zum Zitat American Cancer Society. Cancer facts & figures, 2015. Atlanta American Cancer Society. Cancer facts & figures, 2015. Atlanta
3.
Zurück zum Zitat Vale W, Spiess J, Rivier C, Rivier J (1981) Characterization of a 41-residue ovine hypothalamic peptide that stimulates secretion of corticotropin and beta-endorphin. Science 213:1394–1397PubMedCrossRef Vale W, Spiess J, Rivier C, Rivier J (1981) Characterization of a 41-residue ovine hypothalamic peptide that stimulates secretion of corticotropin and beta-endorphin. Science 213:1394–1397PubMedCrossRef
4.
Zurück zum Zitat Rivier C, Vale W (1983) Modulation of stress-induced ACTH release by corticotropin-releasing factor, catecholamines and vasopressin. Nature 305:325–327PubMedCrossRef Rivier C, Vale W (1983) Modulation of stress-induced ACTH release by corticotropin-releasing factor, catecholamines and vasopressin. Nature 305:325–327PubMedCrossRef
6.
Zurück zum Zitat Endoh A, Kristiansen SB, Casson PR, Buster JE, Hornsby PJ (1996) The zona reticularis is the site of biosynthesis of dehydroepiandrosterone and dehydroepiandrosterone sulfate in the adult human adrenal cortex resulting from its low expression of 3 beta-hydroxysteroid dehydrogenase. J Clin Endocrinol Metab 81:3558–3565. doi:10.1210/jcem.81.10.8855801 PubMed Endoh A, Kristiansen SB, Casson PR, Buster JE, Hornsby PJ (1996) The zona reticularis is the site of biosynthesis of dehydroepiandrosterone and dehydroepiandrosterone sulfate in the adult human adrenal cortex resulting from its low expression of 3 beta-hydroxysteroid dehydrogenase. J Clin Endocrinol Metab 81:3558–3565. doi:10.​1210/​jcem.​81.​10.​8855801 PubMed
8.
Zurück zum Zitat Orentreich N, Brind JL, Rizer RL, Vogelman JH (1984) Age changes and sex differences in serum dehydroepiandrosterone sulfate concentrations throughout adulthood. J Clin Endocrinol Metab 59:551–555. doi:10.1210/jcem-59-3-551 PubMedCrossRef Orentreich N, Brind JL, Rizer RL, Vogelman JH (1984) Age changes and sex differences in serum dehydroepiandrosterone sulfate concentrations throughout adulthood. J Clin Endocrinol Metab 59:551–555. doi:10.​1210/​jcem-59-3-551 PubMedCrossRef
9.
Zurück zum Zitat Rheaume E, Lachance Y, Zhao HF, Breton N, Dumont M, de Launoit Y, Trudel C, Luu-The V, Simard J, Labrie F (1991) Structure and expression of a new complementary DNA encoding the almost exclusive 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4-isomerase in human adrenals and gonads. Mol Endocrinol 5:1147–1157. doi:10.1210/mend-5-8-1147 PubMedCrossRef Rheaume E, Lachance Y, Zhao HF, Breton N, Dumont M, de Launoit Y, Trudel C, Luu-The V, Simard J, Labrie F (1991) Structure and expression of a new complementary DNA encoding the almost exclusive 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4-isomerase in human adrenals and gonads. Mol Endocrinol 5:1147–1157. doi:10.​1210/​mend-5-8-1147 PubMedCrossRef
10.
Zurück zum Zitat Picado-Leonard J, Miller WL (1987) Cloning and sequence of the human gene for P450c17 (steroid 17 alpha-hydroxylase/17,20 lyase): similarity with the gene for P450c21. DNA 6:439–448PubMedCrossRef Picado-Leonard J, Miller WL (1987) Cloning and sequence of the human gene for P450c17 (steroid 17 alpha-hydroxylase/17,20 lyase): similarity with the gene for P450c21. DNA 6:439–448PubMedCrossRef
11.
Zurück zum Zitat Chung BC, Picado-Leonard J, Haniu M, Bienkowski M, Hall PF, Shively JE, Miller WL (1987) Cytochrome P450c17 (steroid 17 alpha-hydroxylase/17,20 lyase): cloning of human adrenal and testis cDNAs indicates the same gene is expressed in both tissues. Proc Natl Acad Sci U S A 84:407–411PubMedPubMedCentralCrossRef Chung BC, Picado-Leonard J, Haniu M, Bienkowski M, Hall PF, Shively JE, Miller WL (1987) Cytochrome P450c17 (steroid 17 alpha-hydroxylase/17,20 lyase): cloning of human adrenal and testis cDNAs indicates the same gene is expressed in both tissues. Proc Natl Acad Sci U S A 84:407–411PubMedPubMedCentralCrossRef
12.
Zurück zum Zitat Matteson KJ, Picado-Leonard J, Chung BC, Mohandas TK, Miller WL (1986) Assignment of the gene for adrenal P450c17 (steroid 17 alpha-hydroxylase/17,20 lyase) to human chromosome 10. J Clin Endocrinol Metab 63:789–791. doi:10.1210/jcem-63-3-789 PubMedCrossRef Matteson KJ, Picado-Leonard J, Chung BC, Mohandas TK, Miller WL (1986) Assignment of the gene for adrenal P450c17 (steroid 17 alpha-hydroxylase/17,20 lyase) to human chromosome 10. J Clin Endocrinol Metab 63:789–791. doi:10.​1210/​jcem-63-3-789 PubMedCrossRef
13.
Zurück zum Zitat Auchus RJ, Lee TC, Miller WL (1998) Cytochrome b5 augments the 17,20-lyase activity of human P450c17 without direct electron transfer. J Biol Chem 273:3158–3165PubMedCrossRef Auchus RJ, Lee TC, Miller WL (1998) Cytochrome b5 augments the 17,20-lyase activity of human P450c17 without direct electron transfer. J Biol Chem 273:3158–3165PubMedCrossRef
14.
Zurück zum Zitat Geller DH, Auchus RJ, Miller WL (1999) P450c17 mutations R347H and R358Q selectively disrupt 17,20-lyase activity by disrupting interactions with P450 oxidoreductase and cytochrome b5. Mol Endocrinol 13:167–175. doi:10.1210/mend.13.1.0219 PubMedCrossRef Geller DH, Auchus RJ, Miller WL (1999) P450c17 mutations R347H and R358Q selectively disrupt 17,20-lyase activity by disrupting interactions with P450 oxidoreductase and cytochrome b5. Mol Endocrinol 13:167–175. doi:10.​1210/​mend.​13.​1.​0219 PubMedCrossRef
15.
Zurück zum Zitat Kominami S, Ogawa N, Morimune R, De-Ying H, Takemori S (1992) The role of cytochrome b5 in adrenal microsomal steroidogenesis. J Steroid Biochem Mol Biol 42:57–64PubMedCrossRef Kominami S, Ogawa N, Morimune R, De-Ying H, Takemori S (1992) The role of cytochrome b5 in adrenal microsomal steroidogenesis. J Steroid Biochem Mol Biol 42:57–64PubMedCrossRef
17.
Zurück zum Zitat Nakamura Y, Hornsby PJ, Casson P, Morimoto R, Satoh F, Xing Y, Kennedy MR, Sasano H, Rainey WE (2009) Type 5 17beta-hydroxysteroid dehydrogenase (AKR1C3) contributes to testosterone production in the adrenal reticularis. J Clin Endocrinol Metab 94:2192–2198. doi:10.1210/jc.2008-2374 PubMedPubMedCentralCrossRef Nakamura Y, Hornsby PJ, Casson P, Morimoto R, Satoh F, Xing Y, Kennedy MR, Sasano H, Rainey WE (2009) Type 5 17beta-hydroxysteroid dehydrogenase (AKR1C3) contributes to testosterone production in the adrenal reticularis. J Clin Endocrinol Metab 94:2192–2198. doi:10.​1210/​jc.​2008-2374 PubMedPubMedCentralCrossRef
18.
Zurück zum Zitat Belchetz PE, Plant TM, Nakai Y, Keogh EJ, Knobil E (1978) Hypophysial responses to continuous and intermittent delivery of hypothalamic gonadotropin-releasing hormone. Science 202:631–633PubMedCrossRef Belchetz PE, Plant TM, Nakai Y, Keogh EJ, Knobil E (1978) Hypophysial responses to continuous and intermittent delivery of hypothalamic gonadotropin-releasing hormone. Science 202:631–633PubMedCrossRef
19.
Zurück zum Zitat Simpson ER, Mahendroo MS, Means GD, Kilgore MW, Hinshelwood MM, Graham-Lorence S, Amarneh B, Ito Y, Fisher CR, Michael MD et al (1994) Aromatase cytochrome P450, the enzyme responsible for estrogen biosynthesis. Endocr Rev 15:342–355. doi:10.1210/edrv-15-3-342 PubMed Simpson ER, Mahendroo MS, Means GD, Kilgore MW, Hinshelwood MM, Graham-Lorence S, Amarneh B, Ito Y, Fisher CR, Michael MD et al (1994) Aromatase cytochrome P450, the enzyme responsible for estrogen biosynthesis. Endocr Rev 15:342–355. doi:10.​1210/​edrv-15-3-342 PubMed
20.
Zurück zum Zitat Luu The V, Labrie C, Zhao HF, Couet J, Lachance Y, Simard J, Leblanc G, Cote J, Berube D, Gagne R et al (1989) Characterization of cDNAs for human estradiol 17 beta-dehydrogenase and assignment of the gene to chromosome 17: evidence of two mRNA species with distinct 5′-termini in human placenta. Mol Endocrinol 3:1301–1309. doi:10.1210/mend-3-8-1301 PubMedCrossRef Luu The V, Labrie C, Zhao HF, Couet J, Lachance Y, Simard J, Leblanc G, Cote J, Berube D, Gagne R et al (1989) Characterization of cDNAs for human estradiol 17 beta-dehydrogenase and assignment of the gene to chromosome 17: evidence of two mRNA species with distinct 5′-termini in human placenta. Mol Endocrinol 3:1301–1309. doi:10.​1210/​mend-3-8-1301 PubMedCrossRef
21.
Zurück zum Zitat Santen RJ (1981) Feedback control of luteinizing hormone and follicle-stimulating hormone secretion by testosterone and estradiol in men: physiological and clinical implications. Clin Biochem 14:243–251PubMedCrossRef Santen RJ (1981) Feedback control of luteinizing hormone and follicle-stimulating hormone secretion by testosterone and estradiol in men: physiological and clinical implications. Clin Biochem 14:243–251PubMedCrossRef
22.
Zurück zum Zitat Meachem SJ, Nieschlag E, Simoni M (2001) Inhibin B in male reproduction: pathophysiology and clinical relevance. Eur J Endocrinol 145:561–571PubMedCrossRef Meachem SJ, Nieschlag E, Simoni M (2001) Inhibin B in male reproduction: pathophysiology and clinical relevance. Eur J Endocrinol 145:561–571PubMedCrossRef
23.
Zurück zum Zitat Sasano H, Okamoto M, Mason JI, Simpson ER, Mendelson CR, Sasano N, Silverberg SG (1989) Immunolocalization of aromatase, 17 alpha-hydroxylase and side-chain-cleavage cytochromes P-450 in the human ovary. J Reprod Fertil 85:163–169PubMedCrossRef Sasano H, Okamoto M, Mason JI, Simpson ER, Mendelson CR, Sasano N, Silverberg SG (1989) Immunolocalization of aromatase, 17 alpha-hydroxylase and side-chain-cleavage cytochromes P-450 in the human ovary. J Reprod Fertil 85:163–169PubMedCrossRef
25.
Zurück zum Zitat Santen RJ, Santner S, Davis B, Veldhuis J, Samojlik E, Ruby E (1978) Aminoglutethimide inhibits extraglandular estrogen production in postmenopausal women with breast carcinoma. J Clin Endocrinol Metab 47:1257–1265. doi:10.1210/jcem-47-6-1257 PubMedCrossRef Santen RJ, Santner S, Davis B, Veldhuis J, Samojlik E, Ruby E (1978) Aminoglutethimide inhibits extraglandular estrogen production in postmenopausal women with breast carcinoma. J Clin Endocrinol Metab 47:1257–1265. doi:10.​1210/​jcem-47-6-1257 PubMedCrossRef
26.
Zurück zum Zitat Dumont M, Luu-The V, Dupont E, Pelletier G, Labrie F (1992) Characterization, expression, and immunohistochemical localization of 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase in human skin. J Invest Dermatol 99:415–421PubMedCrossRef Dumont M, Luu-The V, Dupont E, Pelletier G, Labrie F (1992) Characterization, expression, and immunohistochemical localization of 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase in human skin. J Invest Dermatol 99:415–421PubMedCrossRef
29.
Zurück zum Zitat Judd HL, Judd GE, Lucas WE, Yen SS (1974) Endocrine function of the postmenopausal ovary: concentration of androgens and estrogens in ovarian and peripheral vein blood. J Clin Endocrinol Metab 39:1020–1024. doi:10.1210/jcem-39-6-1020 PubMedCrossRef Judd HL, Judd GE, Lucas WE, Yen SS (1974) Endocrine function of the postmenopausal ovary: concentration of androgens and estrogens in ovarian and peripheral vein blood. J Clin Endocrinol Metab 39:1020–1024. doi:10.​1210/​jcem-39-6-1020 PubMedCrossRef
31.
Zurück zum Zitat Mangelsdorf DJ, Thummel C, Beato M, Herrlich P, Schutz G, Umesono K, Blumberg B, Kastner P, Mark M, Chambon P, Evans RM (1995) The nuclear receptor superfamily: the second decade. Cell 83:835–839PubMedCrossRef Mangelsdorf DJ, Thummel C, Beato M, Herrlich P, Schutz G, Umesono K, Blumberg B, Kastner P, Mark M, Chambon P, Evans RM (1995) The nuclear receptor superfamily: the second decade. Cell 83:835–839PubMedCrossRef
33.
Zurück zum Zitat Wurtz JM, Bourguet W, Renaud JP, Vivat V, Chambon P, Moras D, Gronemeyer H (1996) A canonical structure for the ligand-binding domain of nuclear receptors. Nat Struct Biol 3:87–94PubMedCrossRef Wurtz JM, Bourguet W, Renaud JP, Vivat V, Chambon P, Moras D, Gronemeyer H (1996) A canonical structure for the ligand-binding domain of nuclear receptors. Nat Struct Biol 3:87–94PubMedCrossRef
37.
Zurück zum Zitat Early Breast Cancer Trialists’ Collaborative Group, Dowsett M, Forbes JF, Bradley R, Ingle J, Aihara T, Bliss J, Boccardo F, Coates A, Coombes RC, Cuzick J, Dubsky P, Gnant M, Kaufmann M, Kilburn L, Perrone F, Rea D, Thurlimann B, van de Velde C, Pan H, Peto R, Davies C, Gray R (2015) Aromatase inhibitors versus tamoxifen in early breast cancer: patient-level meta-analysis of the randomised trials. Lancet 386:1341–1352. doi:10.1016/S0140-6736(15)61074-1 CrossRef Early Breast Cancer Trialists’ Collaborative Group, Dowsett M, Forbes JF, Bradley R, Ingle J, Aihara T, Bliss J, Boccardo F, Coates A, Coombes RC, Cuzick J, Dubsky P, Gnant M, Kaufmann M, Kilburn L, Perrone F, Rea D, Thurlimann B, van de Velde C, Pan H, Peto R, Davies C, Gray R (2015) Aromatase inhibitors versus tamoxifen in early breast cancer: patient-level meta-analysis of the randomised trials. Lancet 386:1341–1352. doi:10.​1016/​S0140-6736(15)61074-1 CrossRef
38.
Zurück zum Zitat Ariazi EA, Ariazi JL, Cordera F, Jordan VC (2006) Estrogen receptors as therapeutic targets in breast cancer. Curr Top Med Chem 6:181–202PubMedCrossRef Ariazi EA, Ariazi JL, Cordera F, Jordan VC (2006) Estrogen receptors as therapeutic targets in breast cancer. Curr Top Med Chem 6:181–202PubMedCrossRef
39.
Zurück zum Zitat Winer EP, Hudis C, Burstein HJ, Wolff AC, Pritchard KI, Ingle JN, Chlebowski RT, Gelber R, Edge SB, Gralow J, Cobleigh MA, Mamounas EP, Goldstein LJ, Whelan TJ, Powles TJ, Bryant J, Perkins C, Perotti J, Braun S, Langer AS, Browman GP, Somerfield MR (2005) American Society of Clinical Oncology technology assessment on the use of aromatase inhibitors as adjuvant therapy for postmenopausal women with hormone receptor-positive breast cancer: status report 2004. J Clin Oncol 23:619–629. doi:10.1200/JCO.2005.09.121 PubMedCrossRef Winer EP, Hudis C, Burstein HJ, Wolff AC, Pritchard KI, Ingle JN, Chlebowski RT, Gelber R, Edge SB, Gralow J, Cobleigh MA, Mamounas EP, Goldstein LJ, Whelan TJ, Powles TJ, Bryant J, Perkins C, Perotti J, Braun S, Langer AS, Browman GP, Somerfield MR (2005) American Society of Clinical Oncology technology assessment on the use of aromatase inhibitors as adjuvant therapy for postmenopausal women with hormone receptor-positive breast cancer: status report 2004. J Clin Oncol 23:619–629. doi:10.​1200/​JCO.​2005.​09.​121 PubMedCrossRef
41.
Zurück zum Zitat Dowsett M, Cuzick J, Ingle J, Coates A, Forbes J, Bliss J, Buyse M, Baum M, Buzdar A, Colleoni M, Coombes C, Snowdon C, Gnant M, Jakesz R, Kaufmann M, Boccardo F, Godwin J, Davies C, Peto R (2010) Meta-analysis of breast cancer outcomes in adjuvant trials of aromatase inhibitors versus tamoxifen. J Clin Oncol 28:509–518. doi:10.1200/JCO.2009.23.1274 PubMedCrossRef Dowsett M, Cuzick J, Ingle J, Coates A, Forbes J, Bliss J, Buyse M, Baum M, Buzdar A, Colleoni M, Coombes C, Snowdon C, Gnant M, Jakesz R, Kaufmann M, Boccardo F, Godwin J, Davies C, Peto R (2010) Meta-analysis of breast cancer outcomes in adjuvant trials of aromatase inhibitors versus tamoxifen. J Clin Oncol 28:509–518. doi:10.​1200/​JCO.​2009.​23.​1274 PubMedCrossRef
42.
Zurück zum Zitat Coates AS, Winer EP, Goldhirsch A, Gelber RD, Gnant M, Piccart-Gebhart M, Thurlimann B, Senn HJ, Panel Members (2015) Tailoring therapies-improving the management of early breast cancer: St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2015. Ann Oncol 26:1533–1546. doi:10.1093/annonc/mdv221 PubMedPubMedCentralCrossRef Coates AS, Winer EP, Goldhirsch A, Gelber RD, Gnant M, Piccart-Gebhart M, Thurlimann B, Senn HJ, Panel Members (2015) Tailoring therapies-improving the management of early breast cancer: St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2015. Ann Oncol 26:1533–1546. doi:10.​1093/​annonc/​mdv221 PubMedPubMedCentralCrossRef
43.
Zurück zum Zitat Lippman M, Bolan G, Huff K (1976) The effects of estrogens and antiestrogens on hormone-responsive human breast cancer in long-term tissue culture. Cancer Res 36:4595–4601PubMed Lippman M, Bolan G, Huff K (1976) The effects of estrogens and antiestrogens on hormone-responsive human breast cancer in long-term tissue culture. Cancer Res 36:4595–4601PubMed
44.
Zurück zum Zitat Lippman ME, Bolan G (1975) Oestrogen-responsive human breast cancer in long term tissue culture. Nature 256:592–593PubMedCrossRef Lippman ME, Bolan G (1975) Oestrogen-responsive human breast cancer in long term tissue culture. Nature 256:592–593PubMedCrossRef
45.
Zurück zum Zitat Wells SA Jr, Santen RJ, Lipton A, Haagensen DE Jr, Ruby EJ, Harvey H, Dilley WG (1978) Medical adrenalectomy with aminoglutethimide: clinical studies in postmenopausal patients with metastatic breast carcinoma. Ann Surg 187:475–484PubMedPubMedCentralCrossRef Wells SA Jr, Santen RJ, Lipton A, Haagensen DE Jr, Ruby EJ, Harvey H, Dilley WG (1978) Medical adrenalectomy with aminoglutethimide: clinical studies in postmenopausal patients with metastatic breast carcinoma. Ann Surg 187:475–484PubMedPubMedCentralCrossRef
47.
Zurück zum Zitat Bulun SE, Simpson ER (1994) Competitive reverse transcription-polymerase chain reaction analysis indicates that levels of aromatase cytochrome P450 transcripts in adipose tissue of buttocks, thighs, and abdomen of women increase with advancing age. J Clin Endocrinol Metab 78:428–432. doi:10.1210/jcem.78.2.8106632 PubMed Bulun SE, Simpson ER (1994) Competitive reverse transcription-polymerase chain reaction analysis indicates that levels of aromatase cytochrome P450 transcripts in adipose tissue of buttocks, thighs, and abdomen of women increase with advancing age. J Clin Endocrinol Metab 78:428–432. doi:10.​1210/​jcem.​78.​2.​8106632 PubMed
48.
Zurück zum Zitat Chetrite GS, Cortes-Prieto J, Philippe JC, Wright F, Pasqualini JR (2000) Comparison of estrogen concentrations, estrone sulfatase and aromatase activities in normal, and in cancerous, human breast tissues. J Steroid Biochem Mol Biol 72:23–27PubMedCrossRef Chetrite GS, Cortes-Prieto J, Philippe JC, Wright F, Pasqualini JR (2000) Comparison of estrogen concentrations, estrone sulfatase and aromatase activities in normal, and in cancerous, human breast tissues. J Steroid Biochem Mol Biol 72:23–27PubMedCrossRef
49.
Zurück zum Zitat Santner SJ, Feil PD, Santen RJ (1984) In situ estrogen production via the estrone sulfatase pathway in breast tumors: relative importance versus the aromatase pathway. J Clin Endocrinol Metab 59:29–33. doi:10.1210/jcem-59-1-29 PubMedCrossRef Santner SJ, Feil PD, Santen RJ (1984) In situ estrogen production via the estrone sulfatase pathway in breast tumors: relative importance versus the aromatase pathway. J Clin Endocrinol Metab 59:29–33. doi:10.​1210/​jcem-59-1-29 PubMedCrossRef
50.
Zurück zum Zitat Labrie F, Luu-The V, Lin SX, Simard J, Labrie C, El-Alfy M, Pelletier G, Belanger A (2000) Intracrinology: role of the family of 17 beta-hydroxysteroid dehydrogenases in human physiology and disease. J Mol Endocrinol 25:1–16PubMedCrossRef Labrie F, Luu-The V, Lin SX, Simard J, Labrie C, El-Alfy M, Pelletier G, Belanger A (2000) Intracrinology: role of the family of 17 beta-hydroxysteroid dehydrogenases in human physiology and disease. J Mol Endocrinol 25:1–16PubMedCrossRef
51.
Zurück zum Zitat Key T, Appleby P, Barnes I, Reeves G, Endogenous H, Breast Cancer Collaborative Group (2002) Endogenous sex hormones and breast cancer in postmenopausal women: reanalysis of nine prospective studies. J Natl Cancer Inst 94:606–616PubMedCrossRef Key T, Appleby P, Barnes I, Reeves G, Endogenous H, Breast Cancer Collaborative Group (2002) Endogenous sex hormones and breast cancer in postmenopausal women: reanalysis of nine prospective studies. J Natl Cancer Inst 94:606–616PubMedCrossRef
54.
Zurück zum Zitat Beekman JM, Allan GF, Tsai SY, Tsai MJ, O’Malley BW (1993) Transcriptional activation by the estrogen receptor requires a conformational change in the ligand binding domain. Mol Endocrinol 7:1266–1274. doi:10.1210/mend.7.10.8264659 PubMed Beekman JM, Allan GF, Tsai SY, Tsai MJ, O’Malley BW (1993) Transcriptional activation by the estrogen receptor requires a conformational change in the ligand binding domain. Mol Endocrinol 7:1266–1274. doi:10.​1210/​mend.​7.​10.​8264659 PubMed
55.
Zurück zum Zitat Paige LA, Christensen DJ, Gron H, Norris JD, Gottlin EB, Padilla KM, Chang CY, Ballas LM, Hamilton PT, McDonnell DP, Fowlkes DM (1999) Estrogen receptor (ER) modulators each induce distinct conformational changes in ER alpha and ER beta. Proc Natl Acad Sci U S A 96:3999–4004PubMedPubMedCentralCrossRef Paige LA, Christensen DJ, Gron H, Norris JD, Gottlin EB, Padilla KM, Chang CY, Ballas LM, Hamilton PT, McDonnell DP, Fowlkes DM (1999) Estrogen receptor (ER) modulators each induce distinct conformational changes in ER alpha and ER beta. Proc Natl Acad Sci U S A 96:3999–4004PubMedPubMedCentralCrossRef
56.
Zurück zum Zitat Fisher B, Costantino JP, Wickerham DL, Redmond CK, Kavanah M, Cronin WM, Vogel V, Robidoux A, Dimitrov N, Atkins J, Daly M, Wieand S, Tan-Chiu E, Ford L, Wolmark N (1998) Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J Natl Cancer Inst 90:1371–1388PubMedCrossRef Fisher B, Costantino JP, Wickerham DL, Redmond CK, Kavanah M, Cronin WM, Vogel V, Robidoux A, Dimitrov N, Atkins J, Daly M, Wieand S, Tan-Chiu E, Ford L, Wolmark N (1998) Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J Natl Cancer Inst 90:1371–1388PubMedCrossRef
57.
Zurück zum Zitat Stearns V, Johnson MD, Rae JM, Morocho A, Novielli A, Bhargava P, Hayes DF, Desta Z, Flockhart DA (2003) Active tamoxifen metabolite plasma concentrations after coadministration of tamoxifen and the selective serotonin reuptake inhibitor paroxetine. J Natl Cancer Inst 95:1758–1764PubMedCrossRef Stearns V, Johnson MD, Rae JM, Morocho A, Novielli A, Bhargava P, Hayes DF, Desta Z, Flockhart DA (2003) Active tamoxifen metabolite plasma concentrations after coadministration of tamoxifen and the selective serotonin reuptake inhibitor paroxetine. J Natl Cancer Inst 95:1758–1764PubMedCrossRef
58.
59.
60.
Zurück zum Zitat Gail MH, Costantino JP, Bryant J, Croyle R, Freedman L, Helzlsouer K, Vogel V (1999) Weighing the risks and benefits of tamoxifen treatment for preventing breast cancer. J Natl Cancer Inst 91:1829–1846PubMedCrossRef Gail MH, Costantino JP, Bryant J, Croyle R, Freedman L, Helzlsouer K, Vogel V (1999) Weighing the risks and benefits of tamoxifen treatment for preventing breast cancer. J Natl Cancer Inst 91:1829–1846PubMedCrossRef
61.
Zurück zum Zitat Nicholson RI, Gee JM, Manning DL, Wakeling AE, Montano MM, Katzenellenbogen BS (1995) Responses to pure antiestrogens (ICI 164384, ICI 182780) in estrogen-sensitive and -resistant experimental and clinical breast cancer. Ann N Y Acad Sci 761:148–163PubMedCrossRef Nicholson RI, Gee JM, Manning DL, Wakeling AE, Montano MM, Katzenellenbogen BS (1995) Responses to pure antiestrogens (ICI 164384, ICI 182780) in estrogen-sensitive and -resistant experimental and clinical breast cancer. Ann N Y Acad Sci 761:148–163PubMedCrossRef
62.
Zurück zum Zitat Lai A, Kahraman M, Govek S, Nagasawa J, Bonnefous C, Julien J, Douglas K, Sensintaffar J, Lu N, Lee KJ, Aparicio A, Kaufman J, Qian J, Shao G, Prudente R, Moon MJ, Joseph JD, Darimont B, Brigham D, Grillot K, Heyman R, Rix PJ, Hager JH, Smith ND (2015) Identification of GDC-0810 (ARN-810), an orally bioavailable selective estrogen receptor degrader (SERD) that demonstrates robust activity in tamoxifen-resistant breast cancer xenografts. J Med Chem 58:4888–4904. doi:10.1021/acs.jmedchem.5b00054 PubMedCrossRef Lai A, Kahraman M, Govek S, Nagasawa J, Bonnefous C, Julien J, Douglas K, Sensintaffar J, Lu N, Lee KJ, Aparicio A, Kaufman J, Qian J, Shao G, Prudente R, Moon MJ, Joseph JD, Darimont B, Brigham D, Grillot K, Heyman R, Rix PJ, Hager JH, Smith ND (2015) Identification of GDC-0810 (ARN-810), an orally bioavailable selective estrogen receptor degrader (SERD) that demonstrates robust activity in tamoxifen-resistant breast cancer xenografts. J Med Chem 58:4888–4904. doi:10.​1021/​acs.​jmedchem.​5b00054 PubMedCrossRef
64.
Zurück zum Zitat Smith IE, Harris AL, Morgan M, Ford HT, Gazet JC, Harmer CL, White H, Parsons CA, Villardo A, Walsh G, McKinna JA (1981) Tamoxifen versus aminoglutethimide in advanced breast carcinoma: a randomized cross-over trial. Br Med J (Clin Res Ed) 283:1432–1434CrossRef Smith IE, Harris AL, Morgan M, Ford HT, Gazet JC, Harmer CL, White H, Parsons CA, Villardo A, Walsh G, McKinna JA (1981) Tamoxifen versus aminoglutethimide in advanced breast carcinoma: a randomized cross-over trial. Br Med J (Clin Res Ed) 283:1432–1434CrossRef
65.
Zurück zum Zitat Covey DF, Hood WF, Parikh VD (1981) 10 beta-propynyl-substituted steroids. Mechanism-based enzyme-activated irreversible inhibitors of estrogen biosynthesis. J Biol Chem 256:1076–1079PubMed Covey DF, Hood WF, Parikh VD (1981) 10 beta-propynyl-substituted steroids. Mechanism-based enzyme-activated irreversible inhibitors of estrogen biosynthesis. J Biol Chem 256:1076–1079PubMed
66.
Zurück zum Zitat Siiteri PK, Thompson EA (1975) Studies of human placental aromatase. J Steroid Biochem 6:317–322PubMedCrossRef Siiteri PK, Thompson EA (1975) Studies of human placental aromatase. J Steroid Biochem 6:317–322PubMedCrossRef
67.
Zurück zum Zitat Brodie AM, Schwarzel WC, Shaikh AA, Brodie HJ (1977) The effect of an aromatase inhibitor, 4-hydroxy-4-androstene-3,17-dione, on estrogen-dependent processes in reproduction and breast cancer. Endocrinology 100:1684–1695. doi:10.1210/endo-100-6-1684 PubMedCrossRef Brodie AM, Schwarzel WC, Shaikh AA, Brodie HJ (1977) The effect of an aromatase inhibitor, 4-hydroxy-4-androstene-3,17-dione, on estrogen-dependent processes in reproduction and breast cancer. Endocrinology 100:1684–1695. doi:10.​1210/​endo-100-6-1684 PubMedCrossRef
68.
Zurück zum Zitat Howell A, Cuzick J, Baum M, Buzdar A, Dowsett M, Forbes JF, Hoctin-Boes G, Houghton J, Locker GY, Tobias JS, ATAC Trialists’ Group (2005) Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years’ adjuvant treatment for breast cancer. Lancet 365:60–62. doi:10.1016/s0140-6736(04)17666-6 PubMedCrossRef Howell A, Cuzick J, Baum M, Buzdar A, Dowsett M, Forbes JF, Hoctin-Boes G, Houghton J, Locker GY, Tobias JS, ATAC Trialists’ Group (2005) Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years’ adjuvant treatment for breast cancer. Lancet 365:60–62. doi:10.​1016/​s0140-6736(04)17666-6 PubMedCrossRef
69.
Zurück zum Zitat Breast International Group 1–98 Collaborative Group, Thurlimann B, Keshaviah A, Coates AS, Mouridsen H, Mauriac L, Forbes JF, Paridaens R, Castiglione-Gertsch M, Gelber RD, Rabaglio M, Smith I, Wardley A, Price KN, Goldhirsch A (2005) A comparison of letrozole and tamoxifen in postmenopausal women with early breast cancer. N Engl J Med 353:2747–2757. doi:10.1056/NEJMoa052258 CrossRef Breast International Group 1–98 Collaborative Group, Thurlimann B, Keshaviah A, Coates AS, Mouridsen H, Mauriac L, Forbes JF, Paridaens R, Castiglione-Gertsch M, Gelber RD, Rabaglio M, Smith I, Wardley A, Price KN, Goldhirsch A (2005) A comparison of letrozole and tamoxifen in postmenopausal women with early breast cancer. N Engl J Med 353:2747–2757. doi:10.​1056/​NEJMoa052258 CrossRef
72.
Zurück zum Zitat Huggins C, Hodges CV (1941) Studies on prostatic cancer. I. The effect of castration, of estrogen and androgen injection on serum phosphatases in metastatic carcinoma of the prostate. Cancer Res 22:232–240 Huggins C, Hodges CV (1941) Studies on prostatic cancer. I. The effect of castration, of estrogen and androgen injection on serum phosphatases in metastatic carcinoma of the prostate. Cancer Res 22:232–240
73.
Zurück zum Zitat Mohler JL, Gregory CW, Ford OH 3rd, Kim D, Weaver CM, Petrusz P, Wilson EM, French FS (2004) The androgen axis in recurrent prostate cancer. Clin Cancer Res 10:440–448PubMedCrossRef Mohler JL, Gregory CW, Ford OH 3rd, Kim D, Weaver CM, Petrusz P, Wilson EM, French FS (2004) The androgen axis in recurrent prostate cancer. Clin Cancer Res 10:440–448PubMedCrossRef
75.
Zurück zum Zitat Visakorpi T, Hyytinen E, Koivisto P, Tanner M, Keinanen R, Palmberg C, Palotie A, Tammela T, Isola J, Kallioniemi OP (1995) In vivo amplification of the androgen receptor gene and progression of human prostate cancer. Nat Genet 9:401–406. doi:10.1038/ng0495-401 PubMedCrossRef Visakorpi T, Hyytinen E, Koivisto P, Tanner M, Keinanen R, Palmberg C, Palotie A, Tammela T, Isola J, Kallioniemi OP (1995) In vivo amplification of the androgen receptor gene and progression of human prostate cancer. Nat Genet 9:401–406. doi:10.​1038/​ng0495-401 PubMedCrossRef
76.
Zurück zum Zitat Veldscholte J, Ris-Stalpers C, Kuiper GG, Jenster G, Berrevoets C, Claassen E, van Rooij HC, Trapman J, Brinkmann AO, Mulder E (1990) 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 Commun 173:534–540PubMedCrossRef Veldscholte J, Ris-Stalpers C, Kuiper GG, Jenster G, Berrevoets C, Claassen E, van Rooij HC, Trapman J, Brinkmann AO, Mulder E (1990) 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 Commun 173:534–540PubMedCrossRef
78.
Zurück zum Zitat Belanger B, Belanger A, Labrie F, Dupont A, Cusan L, Monfette G (1989) Comparison of residual C-19 steroids in plasma and prostatic tissue of human, rat and guinea pig after castration: unique importance of extratesticular androgens in men. J Steroid Biochem 32:695–698PubMedCrossRef Belanger B, Belanger A, Labrie F, Dupont A, Cusan L, Monfette G (1989) Comparison of residual C-19 steroids in plasma and prostatic tissue of human, rat and guinea pig after castration: unique importance of extratesticular androgens in men. J Steroid Biochem 32:695–698PubMedCrossRef
79.
Zurück zum Zitat Evaul K, Li R, Papari-Zareei M, Auchus RJ, Sharifi N (2010) 3beta-hydroxysteroid dehydrogenase is a possible pharmacological target in the treatment of castration-resistant prostate cancer. Endocrinology 151:3514–3520. doi:10.1210/en.2010-0138 PubMedCrossRef Evaul K, Li R, Papari-Zareei M, Auchus RJ, Sharifi N (2010) 3beta-hydroxysteroid dehydrogenase is a possible pharmacological target in the treatment of castration-resistant prostate cancer. Endocrinology 151:3514–3520. doi:10.​1210/​en.​2010-0138 PubMedCrossRef
80.
Zurück zum Zitat Li R, Evaul K, Sharma KK, Chang KH, Yoshimoto J, Liu J, Auchus RJ, Sharifi N (2012) Abiraterone inhibits 3beta-hydroxysteroid dehydrogenase: a rationale for increasing drug exposure in castration-resistant prostate cancer. Clin Cancer Res 18:3571–3579. doi:10.1158/1078-0432.ccr-12-0908 PubMedCrossRef Li R, Evaul K, Sharma KK, Chang KH, Yoshimoto J, Liu J, Auchus RJ, Sharifi N (2012) Abiraterone inhibits 3beta-hydroxysteroid dehydrogenase: a rationale for increasing drug exposure in castration-resistant prostate cancer. Clin Cancer Res 18:3571–3579. doi:10.​1158/​1078-0432.​ccr-12-0908 PubMedCrossRef
82.
Zurück zum Zitat Wilson JD, Auchus RJ, Leihy MW, Guryev OL, Estabrook RW, Osborn SM, Shaw G, Renfree MB (2003) 5alpha-androstane-3alpha,17beta-diol is formed in tammar wallaby pouch young testes by a pathway involving 5alpha-pregnane-3alpha,17alpha-diol-20-one as a key intermediate. Endocrinology 144:575–580. doi:10.1210/en.2002-220721 PubMedCrossRef Wilson JD, Auchus RJ, Leihy MW, Guryev OL, Estabrook RW, Osborn SM, Shaw G, Renfree MB (2003) 5alpha-androstane-3alpha,17beta-diol is formed in tammar wallaby pouch young testes by a pathway involving 5alpha-pregnane-3alpha,17alpha-diol-20-one as a key intermediate. Endocrinology 144:575–580. doi:10.​1210/​en.​2002-220721 PubMedCrossRef
85.
Zurück zum Zitat Eisenberger MA, O’Dwyer PJ, Friedman MA (1986) Gonadotropin hormone-releasing hormone analogues: a new therapeutic approach for prostatic carcinoma. J Clin Oncol 4:414–424PubMed Eisenberger MA, O’Dwyer PJ, Friedman MA (1986) Gonadotropin hormone-releasing hormone analogues: a new therapeutic approach for prostatic carcinoma. J Clin Oncol 4:414–424PubMed
86.
Zurück zum Zitat Pagani O, Regan MM, Walley BA, Fleming GF, Colleoni M, Lang I, Gomez HL, Tondini C, Burstein HJ, Perez EA, Ciruelos E, Stearns V, Bonnefoi HR, Martino S, Geyer CE Jr, Pinotti G, Puglisi F, Crivellari D, Ruhstaller T, Winer EP, Rabaglio-Poretti M, Maibach R, Ruepp B, Giobbie-Hurder A, Price KN, Bernhard J, Luo W, Ribi K, Viale G, Coates AS, Gelber RD, Goldhirsch A, Francis PA, TEXT and SOFT Investigators, International Breast Cancer Study Group (2014) Adjuvant exemestane with ovarian suppression in premenopausal breast cancer. N Engl J Med 371:107–118. doi:10.1056/NEJMoa1404037 PubMedPubMedCentralCrossRef Pagani O, Regan MM, Walley BA, Fleming GF, Colleoni M, Lang I, Gomez HL, Tondini C, Burstein HJ, Perez EA, Ciruelos E, Stearns V, Bonnefoi HR, Martino S, Geyer CE Jr, Pinotti G, Puglisi F, Crivellari D, Ruhstaller T, Winer EP, Rabaglio-Poretti M, Maibach R, Ruepp B, Giobbie-Hurder A, Price KN, Bernhard J, Luo W, Ribi K, Viale G, Coates AS, Gelber RD, Goldhirsch A, Francis PA, TEXT and SOFT Investigators, International Breast Cancer Study Group (2014) Adjuvant exemestane with ovarian suppression in premenopausal breast cancer. N Engl J Med 371:107–118. doi:10.​1056/​NEJMoa1404037 PubMedPubMedCentralCrossRef
87.
Zurück zum Zitat Crawford ED, Eisenberger MA, McLeod DG, Spaulding JT, Benson R, Dorr FA, Blumenstein BA, Davis MA, Goodman PJ (1989) A controlled trial of leuprolide with and without flutamide in prostatic carcinoma. N Engl J Med 321:419–424. doi:10.1056/NEJM198908173210702 PubMedCrossRef Crawford ED, Eisenberger MA, McLeod DG, Spaulding JT, Benson R, Dorr FA, Blumenstein BA, Davis MA, Goodman PJ (1989) A controlled trial of leuprolide with and without flutamide in prostatic carcinoma. N Engl J Med 321:419–424. doi:10.​1056/​NEJM198908173210​702 PubMedCrossRef
88.
Zurück zum Zitat Masiello D, Cheng S, Bubley GJ, Lu ML, Balk SP (2002) Bicalutamide functions as an androgen receptor antagonist by assembly of a transcriptionally inactive receptor. J Biol Chem 277:26321–26326. doi:10.1074/jbc.M203310200 PubMedCrossRef Masiello D, Cheng S, Bubley GJ, Lu ML, Balk SP (2002) Bicalutamide functions as an androgen receptor antagonist by assembly of a transcriptionally inactive receptor. J Biol Chem 277:26321–26326. doi:10.​1074/​jbc.​M203310200 PubMedCrossRef
89.
Zurück zum Zitat Singh SM, Gauthier S, Labrie F (2000) Androgen receptor antagonists (antiandrogens): structure-activity relationships. Curr Med Chem 7:211–247PubMedCrossRef Singh SM, Gauthier S, Labrie F (2000) Androgen receptor antagonists (antiandrogens): structure-activity relationships. Curr Med Chem 7:211–247PubMedCrossRef
90.
Zurück zum Zitat Tran C, Ouk S, Clegg NJ, Chen Y, Watson PA, Arora V, Wongvipat J, Smith-Jones PM, Yoo D, Kwon A, Wasielewska T, Welsbie D, Chen CD, Higano CS, Beer TM, Hung DT, Scher HI, Jung ME, Sawyers CL (2009) Development of a second-generation antiandrogen for treatment of advanced prostate cancer. Science 324:787–790. doi:10.1126/science.1168175 PubMedPubMedCentralCrossRef Tran C, Ouk S, Clegg NJ, Chen Y, Watson PA, Arora V, Wongvipat J, Smith-Jones PM, Yoo D, Kwon A, Wasielewska T, Welsbie D, Chen CD, Higano CS, Beer TM, Hung DT, Scher HI, Jung ME, Sawyers CL (2009) Development of a second-generation antiandrogen for treatment of advanced prostate cancer. Science 324:787–790. doi:10.​1126/​science.​1168175 PubMedPubMedCentralCrossRef
91.
Zurück zum Zitat Scher HI, Fizazi K, Saad F, Taplin ME, Sternberg CN, Miller K, de Wit R, Mulders P, Chi KN, Shore ND, Armstrong AJ, Flaig TW, Flechon A, Mainwaring P, Fleming M, Hainsworth JD, Hirmand M, Selby B, Seely L, de Bono JS, Investigators A (2012) Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med 367:1187–1197. doi:10.1056/NEJMoa1207506 PubMedCrossRef Scher HI, Fizazi K, Saad F, Taplin ME, Sternberg CN, Miller K, de Wit R, Mulders P, Chi KN, Shore ND, Armstrong AJ, Flaig TW, Flechon A, Mainwaring P, Fleming M, Hainsworth JD, Hirmand M, Selby B, Seely L, de Bono JS, Investigators A (2012) Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med 367:1187–1197. doi:10.​1056/​NEJMoa1207506 PubMedCrossRef
92.
Zurück zum Zitat Beer TM, Armstrong AJ, Rathkopf DE, Loriot Y, Sternberg CN, Higano CS, Iversen P, Bhattacharya S, Carles J, Chowdhury S, Davis ID, de Bono JS, Evans CP, Fizazi K, Joshua AM, Kim CS, Kimura G, Mainwaring P, Mansbach H, Miller K, Noonberg SB, Perabo F, Phung D, Saad F, Scher HI, Taplin ME, Venner PM, Tombal B, Investigators P (2014) Enzalutamide in metastatic prostate cancer before chemotherapy. N Engl J Med 371:424–433. doi:10.1056/NEJMoa1405095 PubMedPubMedCentralCrossRef Beer TM, Armstrong AJ, Rathkopf DE, Loriot Y, Sternberg CN, Higano CS, Iversen P, Bhattacharya S, Carles J, Chowdhury S, Davis ID, de Bono JS, Evans CP, Fizazi K, Joshua AM, Kim CS, Kimura G, Mainwaring P, Mansbach H, Miller K, Noonberg SB, Perabo F, Phung D, Saad F, Scher HI, Taplin ME, Venner PM, Tombal B, Investigators P (2014) Enzalutamide in metastatic prostate cancer before chemotherapy. N Engl J Med 371:424–433. doi:10.​1056/​NEJMoa1405095 PubMedPubMedCentralCrossRef
94.
95.
Zurück zum Zitat Pont A, Williams PL, Azhar S, Reitz RE, Bochra C, Smith ER, Stevens DA (1982) Ketoconazole blocks testosterone synthesis. Arch Intern Med 142:2137–2140PubMedCrossRef Pont A, Williams PL, Azhar S, Reitz RE, Bochra C, Smith ER, Stevens DA (1982) Ketoconazole blocks testosterone synthesis. Arch Intern Med 142:2137–2140PubMedCrossRef
97.
Zurück zum Zitat Attard G, Reid AH, Auchus RJ, Hughes BA, Cassidy AM, Thompson E, Oommen NB, Folkerd E, Dowsett M, Arlt W, de Bono JS (2012) Clinical and biochemical consequences of CYP17A1 inhibition with abiraterone given with and without exogenous glucocorticoids in castrate men with advanced prostate cancer. J Clin Endocrinol Metab 97:507–516. doi:10.1210/jc.2011-2189 PubMedCrossRef Attard G, Reid AH, Auchus RJ, Hughes BA, Cassidy AM, Thompson E, Oommen NB, Folkerd E, Dowsett M, Arlt W, de Bono JS (2012) Clinical and biochemical consequences of CYP17A1 inhibition with abiraterone given with and without exogenous glucocorticoids in castrate men with advanced prostate cancer. J Clin Endocrinol Metab 97:507–516. doi:10.​1210/​jc.​2011-2189 PubMedCrossRef
98.
Zurück zum Zitat Costa-Santos M, Kater CE, Auchus RJ, Brazilian Congenital Adrenal Hyperplasia Multicenter Study Group (2004) Two prevalent CYP17 mutations and genotype-phenotype correlations in 24 Brazilian patients with 17-hydroxylase deficiency. J Clin Endocrinol Metab 89:49–60. doi:10.1210/jc.2003-031021 PubMedCrossRef Costa-Santos M, Kater CE, Auchus RJ, Brazilian Congenital Adrenal Hyperplasia Multicenter Study Group (2004) Two prevalent CYP17 mutations and genotype-phenotype correlations in 24 Brazilian patients with 17-hydroxylase deficiency. J Clin Endocrinol Metab 89:49–60. doi:10.​1210/​jc.​2003-031021 PubMedCrossRef
99.
Zurück zum Zitat Attard G, Reid AH, Yap TA, Raynaud F, Dowsett M, Settatree S, Barrett M, Parker C, Martins V, Folkerd E, Clark J, Cooper CS, Kaye SB, Dearnaley D, Lee G, de Bono JS (2008) Phase I clinical trial of a selective inhibitor of CYP17, abiraterone acetate, confirms that castration-resistant prostate cancer commonly remains hormone driven. J Clin Oncol 26:4563–4571. doi:10.1200/jco.2007.15.9749 PubMedCrossRef Attard G, Reid AH, Yap TA, Raynaud F, Dowsett M, Settatree S, Barrett M, Parker C, Martins V, Folkerd E, Clark J, Cooper CS, Kaye SB, Dearnaley D, Lee G, de Bono JS (2008) Phase I clinical trial of a selective inhibitor of CYP17, abiraterone acetate, confirms that castration-resistant prostate cancer commonly remains hormone driven. J Clin Oncol 26:4563–4571. doi:10.​1200/​jco.​2007.​15.​9749 PubMedCrossRef
100.
Zurück zum Zitat de Bono JS, Logothetis CJ, Molina A, Fizazi K, North S, Chu L, Chi KN, Jones RJ, Goodman OB Jr, Saad F, Staffurth JN, Mainwaring P, Harland S, Flaig TW, Hutson TE, Cheng T, Patterson H, Hainsworth JD, Ryan CJ, Sternberg CN, Ellard SL, Flechon A, Saleh M, Scholz M, Efstathiou E, Zivi A, Bianchini D, Loriot Y, Chieffo N, Kheoh T, Haqq CM, Scher HI, COU-AA-301 Investigators (2011) Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med 364:1995–2005. doi:10.1056/NEJMoa1014618 PubMedPubMedCentralCrossRef de Bono JS, Logothetis CJ, Molina A, Fizazi K, North S, Chu L, Chi KN, Jones RJ, Goodman OB Jr, Saad F, Staffurth JN, Mainwaring P, Harland S, Flaig TW, Hutson TE, Cheng T, Patterson H, Hainsworth JD, Ryan CJ, Sternberg CN, Ellard SL, Flechon A, Saleh M, Scholz M, Efstathiou E, Zivi A, Bianchini D, Loriot Y, Chieffo N, Kheoh T, Haqq CM, Scher HI, COU-AA-301 Investigators (2011) Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med 364:1995–2005. doi:10.​1056/​NEJMoa1014618 PubMedPubMedCentralCrossRef
101.
Zurück zum Zitat Ryan CJ, Smith MR, de Bono JS, Molina A, Logothetis CJ, de Souza P, Fizazi K, Mainwaring P, Piulats JM, Ng S, Carles J, Mulders PF, Basch E, Small EJ, Saad F, Schrijvers D, Van Poppel H, Mukherjee SD, Suttmann H, Gerritsen WR, Flaig TW, George DJ, Yu EY, Efstathiou E, Pantuck A, Winquist E, Higano CS, Taplin ME, Park Y, Kheoh T, Griffin T, Scher HI, Rathkopf DE, COU-AA-302 Investigators (2013) Abiraterone in metastatic prostate cancer without previous chemotherapy. N Engl J Med 368:138–148. doi:10.1056/NEJMoa1209096 PubMedPubMedCentralCrossRef Ryan CJ, Smith MR, de Bono JS, Molina A, Logothetis CJ, de Souza P, Fizazi K, Mainwaring P, Piulats JM, Ng S, Carles J, Mulders PF, Basch E, Small EJ, Saad F, Schrijvers D, Van Poppel H, Mukherjee SD, Suttmann H, Gerritsen WR, Flaig TW, George DJ, Yu EY, Efstathiou E, Pantuck A, Winquist E, Higano CS, Taplin ME, Park Y, Kheoh T, Griffin T, Scher HI, Rathkopf DE, COU-AA-302 Investigators (2013) Abiraterone in metastatic prostate cancer without previous chemotherapy. N Engl J Med 368:138–148. doi:10.​1056/​NEJMoa1209096 PubMedPubMedCentralCrossRef
102.
Zurück zum Zitat Richards J, Lim AC, Hay CW, Taylor AE, Wingate A, Nowakowska K, Pezaro C, Carreira S, Goodall J, Arlt W, McEwan IJ, de Bono JS, Attard G (2012) Interactions of abiraterone, eplerenone, and prednisolone with wild-type and mutant androgen receptor: a rationale for increasing abiraterone exposure or combining with MDV3100. Cancer Res 72:2176–2182. doi:10.1158/0008-5472.can-11-3980 PubMedPubMedCentralCrossRef Richards J, Lim AC, Hay CW, Taylor AE, Wingate A, Nowakowska K, Pezaro C, Carreira S, Goodall J, Arlt W, McEwan IJ, de Bono JS, Attard G (2012) Interactions of abiraterone, eplerenone, and prednisolone with wild-type and mutant androgen receptor: a rationale for increasing abiraterone exposure or combining with MDV3100. Cancer Res 72:2176–2182. doi:10.​1158/​0008-5472.​can-11-3980 PubMedPubMedCentralCrossRef
104.
Zurück zum Zitat Handratta VD, Vasaitis TS, Njar VC, Gediya LK, Kataria R, Chopra P, Newman D Jr, Farquhar R, Guo Z, Qiu Y, Brodie AM (2005) Novel C-17-heteroaryl steroidal CYP17 inhibitors/antiandrogens: synthesis, in vitro biological activity, pharmacokinetics, and antitumor activity in the LAPC4 human prostate cancer xenograft model. J Med Chem 48:2972–2984. doi:10.1021/jm040202w PubMedCrossRef Handratta VD, Vasaitis TS, Njar VC, Gediya LK, Kataria R, Chopra P, Newman D Jr, Farquhar R, Guo Z, Qiu Y, Brodie AM (2005) Novel C-17-heteroaryl steroidal CYP17 inhibitors/antiandrogens: synthesis, in vitro biological activity, pharmacokinetics, and antitumor activity in the LAPC4 human prostate cancer xenograft model. J Med Chem 48:2972–2984. doi:10.​1021/​jm040202w PubMedCrossRef
105.
Zurück zum Zitat Kwegyir-Afful AK, Ramalingam S, Purushottamachar P, Ramamurthy VP, Njar VC (2015) Galeterone and VNPT55 induce proteasomal degradation of AR/AR-V7, induce significant apoptosis via cytochrome c release and suppress growth of castration resistant prostate cancer xenografts in vivo. Oncotarget 6:27440–27460. doi:10.18632/oncotarget.4578 PubMedPubMedCentralCrossRef Kwegyir-Afful AK, Ramalingam S, Purushottamachar P, Ramamurthy VP, Njar VC (2015) Galeterone and VNPT55 induce proteasomal degradation of AR/AR-V7, induce significant apoptosis via cytochrome c release and suppress growth of castration resistant prostate cancer xenografts in vivo. Oncotarget 6:27440–27460. doi:10.​18632/​oncotarget.​4578 PubMedPubMedCentralCrossRef
106.
Zurück zum Zitat Montgomery B, Eisenberger MA, Rettig MB, Chu FM, Pili R, Stephenson J, Vogelzang NJ, Koletsky AJ, Nordquist LT, Edenfield WJ, Mamlouk K, Ferrante KJ, Taplin ME (2015) Androgen receptor modulation optimized for response (ARMOR) phase I and II studies: galeterone for the treatment of castration-resistant prostate cancer. Clin Cancer Res. doi:10.1158/1078-0432.CCR-15-1432 PubMedCentral Montgomery B, Eisenberger MA, Rettig MB, Chu FM, Pili R, Stephenson J, Vogelzang NJ, Koletsky AJ, Nordquist LT, Edenfield WJ, Mamlouk K, Ferrante KJ, Taplin ME (2015) Androgen receptor modulation optimized for response (ARMOR) phase I and II studies: galeterone for the treatment of castration-resistant prostate cancer. Clin Cancer Res. doi:10.​1158/​1078-0432.​CCR-15-1432 PubMedCentral
107.
Zurück zum Zitat Toren PJ, Kim S, Pham S, Mangalji A, Adomat H, Guns EST, Zoubeidi A, Moore W, Gleave ME (2015) Anticancer activity of a novel selective CYP17A1 inhibitor in preclinical models of castrate-resistant prostate cancer. Mol Cancer Ther 14:59–69. doi:10.1158/1535-7163.mct-14-0521 PubMedCrossRef Toren PJ, Kim S, Pham S, Mangalji A, Adomat H, Guns EST, Zoubeidi A, Moore W, Gleave ME (2015) Anticancer activity of a novel selective CYP17A1 inhibitor in preclinical models of castrate-resistant prostate cancer. Mol Cancer Ther 14:59–69. doi:10.​1158/​1535-7163.​mct-14-0521 PubMedCrossRef
108.
Zurück zum Zitat Yamaoka M, Hara T, Hitaka T, Kaku T, Takeuchi T, Takahashi J, Asahi S, Miki H, Tasaka A, Kusaka M (2012) Orteronel (TAK-700), a novel non-steroidal 17,20-lyase inhibitor: effects on steroid synthesis in human and monkey adrenal cells and serum steroid levels in cynomolgus monkeys. J Steroid Biochem Mol Biol 129:115–128. doi:10.1016/j.jsbmb.2012.01.001 PubMedCrossRef Yamaoka M, Hara T, Hitaka T, Kaku T, Takeuchi T, Takahashi J, Asahi S, Miki H, Tasaka A, Kusaka M (2012) Orteronel (TAK-700), a novel non-steroidal 17,20-lyase inhibitor: effects on steroid synthesis in human and monkey adrenal cells and serum steroid levels in cynomolgus monkeys. J Steroid Biochem Mol Biol 129:115–128. doi:10.​1016/​j.​jsbmb.​2012.​01.​001 PubMedCrossRef
109.
Zurück zum Zitat Fizazi K, Jones R, Oudard S, Efstathiou E, Saad F, de Wit R, De Bono J, Cruz FM, Fountzilas G, Ulys A, Carcano F, Agarwal N, Agus D, Bellmunt J, Petrylak DP, Lee SY, Webb IJ, Tejura B, Borgstein N, Dreicer R (2015) Phase III, randomized, double-blind, multicenter trial comparing orteronel (TAK-700) plus prednisone with placebo plus prednisone in patients with metastatic castration-resistant prostate cancer that has progressed during or after docetaxel-based therapy: ELM-PC 5. J Clin Oncol 33:723–731. doi:10.1200/JCO.2014.56.5119 PubMedCrossRef Fizazi K, Jones R, Oudard S, Efstathiou E, Saad F, de Wit R, De Bono J, Cruz FM, Fountzilas G, Ulys A, Carcano F, Agarwal N, Agus D, Bellmunt J, Petrylak DP, Lee SY, Webb IJ, Tejura B, Borgstein N, Dreicer R (2015) Phase III, randomized, double-blind, multicenter trial comparing orteronel (TAK-700) plus prednisone with placebo plus prednisone in patients with metastatic castration-resistant prostate cancer that has progressed during or after docetaxel-based therapy: ELM-PC 5. J Clin Oncol 33:723–731. doi:10.​1200/​JCO.​2014.​56.​5119 PubMedCrossRef
110.
Zurück zum Zitat Thompson IM, Goodman PJ, Tangen CM, Lucia MS, Miller GJ, Ford LG, Lieber MM, Cespedes RD, Atkins JN, Lippman SM, Carlin SM, Ryan A, Szczepanek CM, Crowley JJ, Coltman CA Jr (2003) The influence of finasteride on the development of prostate cancer. N Engl J Med 349:215–224. doi:10.1056/NEJMoa030660 PubMedCrossRef Thompson IM, Goodman PJ, Tangen CM, Lucia MS, Miller GJ, Ford LG, Lieber MM, Cespedes RD, Atkins JN, Lippman SM, Carlin SM, Ryan A, Szczepanek CM, Crowley JJ, Coltman CA Jr (2003) The influence of finasteride on the development of prostate cancer. N Engl J Med 349:215–224. doi:10.​1056/​NEJMoa030660 PubMedCrossRef
111.
Zurück zum Zitat Sikora MJ, Cordero KE, Larios JM, Johnson MD, Lippman ME, Rae JM (2009) The androgen metabolite 5alpha-androstane-3beta,17beta-diol (3betaAdiol) induces breast cancer growth via estrogen receptor: implications for aromatase inhibitor resistance. Breast Cancer Res Treat 115:289–296. doi:10.1007/s10549-008-0080-8 PubMedPubMedCentralCrossRef Sikora MJ, Cordero KE, Larios JM, Johnson MD, Lippman ME, Rae JM (2009) The androgen metabolite 5alpha-androstane-3beta,17beta-diol (3betaAdiol) induces breast cancer growth via estrogen receptor: implications for aromatase inhibitor resistance. Breast Cancer Res Treat 115:289–296. doi:10.​1007/​s10549-008-0080-8 PubMedPubMedCentralCrossRef
112.
Zurück zum Zitat Cali JJ, Russell DW (1991) Characterization of human sterol 27-hydroxylase. A mitochondrial cytochrome P-450 that catalyzes multiple oxidation reaction in bile acid biosynthesis. J Biol Chem 266:7774–7778PubMed Cali JJ, Russell DW (1991) Characterization of human sterol 27-hydroxylase. A mitochondrial cytochrome P-450 that catalyzes multiple oxidation reaction in bile acid biosynthesis. J Biol Chem 266:7774–7778PubMed
113.
Zurück zum Zitat Umetani M, Domoto H, Gormley AK, Yuhanna IS, Cummins CL, Javitt NB, Korach KS, Shaul PW, Mangelsdorf DJ (2007) 27-Hydroxycholesterol is an endogenous SERM that inhibits the cardiovascular effects of estrogen. Nat Med 13:1185–1192. doi:10.1038/nm1641 PubMedCrossRef Umetani M, Domoto H, Gormley AK, Yuhanna IS, Cummins CL, Javitt NB, Korach KS, Shaul PW, Mangelsdorf DJ (2007) 27-Hydroxycholesterol is an endogenous SERM that inhibits the cardiovascular effects of estrogen. Nat Med 13:1185–1192. doi:10.​1038/​nm1641 PubMedCrossRef
115.
Zurück zum Zitat Toy W, Shen Y, Won H, Green B, Sakr RA, Will M, Li Z, Gala K, Fanning S, King TA, Hudis C, Chen D, Taran T, Hortobagyi G, Greene G, Berger M, Baselga J, Chandarlapaty S (2013) ESR1 ligand-binding domain mutations in hormone-resistant breast cancer. Nat Genet 45:1439–1445. doi:10.1038/ng.2822 PubMedPubMedCentralCrossRef Toy W, Shen Y, Won H, Green B, Sakr RA, Will M, Li Z, Gala K, Fanning S, King TA, Hudis C, Chen D, Taran T, Hortobagyi G, Greene G, Berger M, Baselga J, Chandarlapaty S (2013) ESR1 ligand-binding domain mutations in hormone-resistant breast cancer. Nat Genet 45:1439–1445. doi:10.​1038/​ng.​2822 PubMedPubMedCentralCrossRef
116.
Zurück zum Zitat Robinson DR, Wu YM, Vats P, Su F, Lonigro RJ, Cao X, Kalyana-Sundaram S, Wang R, Ning Y, Hodges L, Gursky A, Siddiqui J, Tomlins SA, Roychowdhury S, Pienta KJ, Kim SY, Roberts JS, Rae JM, Van Poznak CH, Hayes DF, Chugh R, Kunju LP, Talpaz M, Schott AF, Chinnaiyan AM (2013) Activating ESR1 mutations in hormone-resistant metastatic breast cancer. Nat Genet 45:1446–1451. doi:10.1038/ng.2823 PubMedPubMedCentralCrossRef Robinson DR, Wu YM, Vats P, Su F, Lonigro RJ, Cao X, Kalyana-Sundaram S, Wang R, Ning Y, Hodges L, Gursky A, Siddiqui J, Tomlins SA, Roychowdhury S, Pienta KJ, Kim SY, Roberts JS, Rae JM, Van Poznak CH, Hayes DF, Chugh R, Kunju LP, Talpaz M, Schott AF, Chinnaiyan AM (2013) Activating ESR1 mutations in hormone-resistant metastatic breast cancer. Nat Genet 45:1446–1451. doi:10.​1038/​ng.​2823 PubMedPubMedCentralCrossRef
117.
Zurück zum Zitat Fujii R, Hanamura T, Suzuki T, Gohno T, Shibahara Y, Niwa T, Yamaguchi Y, Ohnuki K, Kakugawa Y, Hirakawa H, Ishida T, Sasano H, Ohuchi N, Hayashi S (2014) Increased androgen receptor activity and cell proliferation in aromatase inhibitor-resistant breast carcinoma. J Steroid Biochem Mol Biol 144 Pt B:513–522. doi:10.1016/j.jsbmb.2014.08.019 PubMedCrossRef Fujii R, Hanamura T, Suzuki T, Gohno T, Shibahara Y, Niwa T, Yamaguchi Y, Ohnuki K, Kakugawa Y, Hirakawa H, Ishida T, Sasano H, Ohuchi N, Hayashi S (2014) Increased androgen receptor activity and cell proliferation in aromatase inhibitor-resistant breast carcinoma. J Steroid Biochem Mol Biol 144 Pt B:513–522. doi:10.​1016/​j.​jsbmb.​2014.​08.​019 PubMedCrossRef
118.
Zurück zum Zitat Rossi E, Morabito A, Di Rella F, Esposito G, Gravina A, Labonia V, Landi G, Nuzzo F, Pacilio C, De Maio E, Di Maio M, Piccirillo MC, De Feo G, D’Aiuto G, Botti G, Chiodini P, Gallo C, Perrone F, de Matteis A (2009) Endocrine effects of adjuvant letrozole compared with tamoxifen in hormone-responsive postmenopausal patients with early breast cancer: the HOBOE trial. J Clin Oncol 27:3192–3197. doi:10.1200/JCO.2008.18.6213 PubMedCrossRef Rossi E, Morabito A, Di Rella F, Esposito G, Gravina A, Labonia V, Landi G, Nuzzo F, Pacilio C, De Maio E, Di Maio M, Piccirillo MC, De Feo G, D’Aiuto G, Botti G, Chiodini P, Gallo C, Perrone F, de Matteis A (2009) Endocrine effects of adjuvant letrozole compared with tamoxifen in hormone-responsive postmenopausal patients with early breast cancer: the HOBOE trial. J Clin Oncol 27:3192–3197. doi:10.​1200/​JCO.​2008.​18.​6213 PubMedCrossRef
119.
Zurück zum Zitat O’Shaughnessy J, Campone M, Brain E, Neven P, Hayes D, Bondarenko I, Griffin TW, Martin J, De Porre P, Kheoh T, Yu MK, Peng W, Johnston S (2015) Abiraterone acetate, exemestane or the combination in postmenopausal patients with estrogen receptor-positive metastatic breast cancer. Ann Oncol 27:106–113. doi:10.1093/annonc/mdv487 PubMedPubMedCentralCrossRef O’Shaughnessy J, Campone M, Brain E, Neven P, Hayes D, Bondarenko I, Griffin TW, Martin J, De Porre P, Kheoh T, Yu MK, Peng W, Johnston S (2015) Abiraterone acetate, exemestane or the combination in postmenopausal patients with estrogen receptor-positive metastatic breast cancer. Ann Oncol 27:106–113. doi:10.​1093/​annonc/​mdv487 PubMedPubMedCentralCrossRef
121.
Zurück zum Zitat Lehmann BD, Bauer JA, Chen X, Sanders ME, Chakravarthy AB, Shyr Y, Pietenpol JA (2011) Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Invest 121:2750–2767. doi:10.1172/jci45014 PubMedPubMedCentralCrossRef Lehmann BD, Bauer JA, Chen X, Sanders ME, Chakravarthy AB, Shyr Y, Pietenpol JA (2011) Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Invest 121:2750–2767. doi:10.​1172/​jci45014 PubMedPubMedCentralCrossRef
123.
125.
Zurück zum Zitat Arce-Salinas C, Riesco-Martinez MC, Hanna W, Bedard P, Warner E (2014) Complete response of metastatic androgen receptor-positive breast cancer to bicalutamide: case report and review of the literature. J Clin Oncol. doi:10.1200/jco.2013.49.8899 PubMed Arce-Salinas C, Riesco-Martinez MC, Hanna W, Bedard P, Warner E (2014) Complete response of metastatic androgen receptor-positive breast cancer to bicalutamide: case report and review of the literature. J Clin Oncol. doi:10.​1200/​jco.​2013.​49.​8899 PubMed
126.
Zurück zum Zitat Gucalp A, Tolaney S, Isakoff SJ, Ingle JN, Liu MC, Carey LA, Blackwell K, Rugo H, Nabell L, Forero A, Stearns V, Doane AS, Danso M, Moynahan ME, Momen LF, Gonzalez JM, Akhtar A, Giri DD, Patil S, Feigin KN, Hudis CA, Traina TA, Translational Breast Cancer Research C (2013) Phase II trial of bicalutamide in patients with androgen receptor-positive, estrogen receptor-negative metastatic breast cancer. Clin Cancer Res 19:5505–5512. doi:10.1158/1078-0432.ccr-12-3327 PubMedPubMedCentralCrossRef Gucalp A, Tolaney S, Isakoff SJ, Ingle JN, Liu MC, Carey LA, Blackwell K, Rugo H, Nabell L, Forero A, Stearns V, Doane AS, Danso M, Moynahan ME, Momen LF, Gonzalez JM, Akhtar A, Giri DD, Patil S, Feigin KN, Hudis CA, Traina TA, Translational Breast Cancer Research C (2013) Phase II trial of bicalutamide in patients with androgen receptor-positive, estrogen receptor-negative metastatic breast cancer. Clin Cancer Res 19:5505–5512. doi:10.​1158/​1078-0432.​ccr-12-3327 PubMedPubMedCentralCrossRef
127.
Zurück zum Zitat Cochrane DR, Bernales S, Jacobsen BM, Cittelly DM, Howe EN, D’Amato NC, Spoelstra NS, Edgerton SM, Jean A, Guerrero J, Gomez F, Medicherla S, Alfaro IE, McCullagh E, Jedlicka P, Torkko KC, Thor AD, Elias AD, Protter AA, Richer JK (2014) Role of the androgen receptor in breast cancer and preclinical analysis of enzalutamide. Breast Cancer Res 16:R7. doi:10.1186/bcr3599 PubMedPubMedCentralCrossRef Cochrane DR, Bernales S, Jacobsen BM, Cittelly DM, Howe EN, D’Amato NC, Spoelstra NS, Edgerton SM, Jean A, Guerrero J, Gomez F, Medicherla S, Alfaro IE, McCullagh E, Jedlicka P, Torkko KC, Thor AD, Elias AD, Protter AA, Richer JK (2014) Role of the androgen receptor in breast cancer and preclinical analysis of enzalutamide. Breast Cancer Res 16:R7. doi:10.​1186/​bcr3599 PubMedPubMedCentralCrossRef
128.
Zurück zum Zitat Traina TA, Miller K, Yardley DA, O’Shaughnessy J, Cortes J, Awada A, Kelly CM, Trudeau ME, Schmid P, Gianni L, Garcia-Estevez L, Nanda R, Ademuyiwa FO, Chan S, Steinberg JL, Blaney ME, Tudor IC, Uppal H, Peterson AC, Hudis CA (2015) Results from a phase 2 study of enzalutamide (ENZA), an androgen receptor (AR) inhibitor, in advanced AR+ triple-negative breast cancer (TNBC). ASCO Meeting Abstracts 33:1003 Traina TA, Miller K, Yardley DA, O’Shaughnessy J, Cortes J, Awada A, Kelly CM, Trudeau ME, Schmid P, Gianni L, Garcia-Estevez L, Nanda R, Ademuyiwa FO, Chan S, Steinberg JL, Blaney ME, Tudor IC, Uppal H, Peterson AC, Hudis CA (2015) Results from a phase 2 study of enzalutamide (ENZA), an androgen receptor (AR) inhibitor, in advanced AR+ triple-negative breast cancer (TNBC). ASCO Meeting Abstracts 33:1003
Metadaten
Titel
The Metabolism, Analysis, and Targeting of Steroid Hormones in Breast and Prostate Cancer
verfasst von
Cameron P. Capper
James M. Rae
Richard J. Auchus
Publikationsdatum
11.03.2016
Verlag
Springer US
Erschienen in
Discover Oncology / Ausgabe 3/2016
Print ISSN: 1868-8497
Elektronische ISSN: 2730-6011
DOI
https://doi.org/10.1007/s12672-016-0259-0

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