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2022], 'Eisenberger,': [42], 'and': [43, 170, 198, 218, 230, 243, 284, 288, 307, 343, 355, 447, 499, 513, 545, 572, 648, 695, 720, 788, 866, 883, 901, 942, 961, 999, 1024, 1079, 1217, 1266, 1367, 1379, 1384, 1425, 1455, 1481, 1528, 1590, 1637, 1651, 1690, 1698, 1846, 1861, 1891, 1951], 'Fernand': [44, 171, 943, 2039], 'Labrie': [45, 173, 2040], 'CrawfordE.': [48], 'Crawford': [50, 1872], 'University': [51, 81, 112, 148, 1873, 1922, 1966, 2011], 'Colorado-Denver,': [53, 1875], 'Aurora,': [54, 1876], 'Colorado': [55, 1877], ',': [56, 68, 87, 101, 117, 129, 140, 153, 169], 'SchellhammerPaul': [59], 'Schellhammer': [61, 1900], 'Eastern': [62, 1901], 'Virginia': [63, 67, 1902, 1906], 'Medical': [64, 1903], 'School,': [65, 1904], 'Norfolk,': [66, 1905], 'McLeodDavid': [71], 'McLeod': [73, 1914], 'Center': [74, 163, 1915, 2028], 'for': [75, 235, 250, 272, 320, 450, 490, 611, 832, 1057, 1082, 1272, 1499, 1550, 1916], 'Disease': [77, 1918], 'Research,': [78, 1691, 1847, 1919], 'Uniformed': [79, 1920], 'Services': [80, 1921], 'the': [83, 195, 204, 216, 224, 239, 268, 314, 337, 375, 396, 414, 497, 503, 535, 543, 583, 612, 737, 772, 919, 974, 1159, 1213, 1244, 1300, 1404, 1423, 1437, 1500, 1508, 1532, 1547, 1608, 1614, 1628, 1670, 1924], 'Health': [84, 1925], 'Sciences,': [85, 1926], 'Bethesda': [86, 1927], 'MoulJudd': [90], 'Moul': [92, 1935], 'Duke': [93, 96, 1936, 1939], 'Cancer': [94, 109, 146, 162, 585, 668, 1136, 1164, 1248, 1387, 1555, 1937, 1963, 2009, 2027], 'Institute,': [95, 1938], 'University,': [97, 1940], 'Durham,': [98, 1941], 'North': [99, 1942], 'Carolina': [100, 121, 128, 1943, 1978, 1985], 'HiganoCelestia': [104], 'Higano': [106, 1960], 'Fred': [107, 1961], 'Hutchinson': [108, 1962], 'Research': [110, 123, 1551, 1964, 1980], 'Center,': [111, 124, 147, 1965, 1981, 2010], 'Washington,': [114, 1968], 'Seattle,': [115, 1969], 'Washington': [116, 1970], 'ShoreNeal': [119], 'Shore': [120, 1977], 'Urologic': [122, 1979], 'Myrtle': [125, 1982], 'Beach,': [126, 1983], 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1039, 1059, 1084, 1103, 1127, 1186, 1220, 1239, 1276, 1298, 1318, 1333, 1352, 1376, 1408, 1441, 1465, 1503, 1573], 'cancer.': [208, 228, 277, 433, 482, 564, 598, 616, 667, 837, 871, 1007, 1060, 1085, 1104, 1221, 1319, 1409], 'This': [209, 252], 'review': [210], 'provides': [211], 'a': [212, 255, 359, 475, 829, 853, 1108, 1132, 1148, 1251, 1279, 1400, 1431, 1541, 1746], 'historical': [213, 1041], 'perspective': [214], 'on': [215, 562, 576, 752, 1505, 1552], 'development': [217, 514, 594], 'clinical': [219, 236, 258, 332, 379, 521], 'benefit': [220], 'antiandrogens': [222, 242, 271, 297, 342, 363, 420, 518], 'Materials': [229, 1835], 'Methods:': [231], 'We': [232], 'searched': [233], 'PubMed®': [234], 'trials': [237, 380], 'search': [240], 'terms': [241], 'cancer': [245, 388, 460, 492, 508, 539, 894, 960, 1023, 1277, 1334, 1353, 1377, 1442, 1504, 1574], 'combined': [246, 328, 642, 807, 1077], 'drug': [248, 448, 1025], 'names': [249], 'antiandrogens.': [251], 'article': [253], 'represents': [254], 'collaboration': [256], 'investigators': [259], 'who': [260], 'made': [262], 'critical': [263], 'scientific': [264], 'contributions': [265], 'leading': [266], 'approval': [269, 397], 'treating': [273], 'patients': [274, 382, 479, 524, 550, 888, 1154, 1181, 1233, 1273, 1460], 'Results:': [278], 'differ': [280], 'chemical': [282], 'structure': [283, 354], 'exert': [285], 'varying': [286], 'efficacy': [287], 'safety': [289, 884, 1267, 1424, 1456], 'profiles.': [290], 'The': [291, 566, 593, 660, 690, 709, 1161, 1742], 'unfavorable': [292], 'therapeutic': [293, 962], 'index': [294], 'steroidal': [296], 'led': [298, 394], 'replacement': [300], 'by': [301, 624, 680, 697, 715, 1685, 1841, 1864, 1895, 1909, 1930, 1955, 1973, 1988, 2002, 2018, 2036, 2048], 'safer': [302], 'nonsteroidal': [303, 1150], 'agents.': [304], 'Flutamide,': [305], 'nilutamide': [306], 'bicalutamide,': [308], 'which': [309, 393], 'were': [310, 317, 334], 'designed': [311, 368], 'target': [313], 'receptor,': [316], 'developed': [318], 'primarily': [319], 'use': [321], 'combination': [323, 338, 1578], 'castration': [325, 344, 346, 385, 457, 464, 1179, 1211], 'provide': [327, 370, 810], 'blockade.': [330], 'Modest': [331], 'benefits': [333, 489], 'observed': [335], 'first': [340], 'generation': [341, 361, 419], 'vs': [345], 'alone.': [347], 'With': [348], 'increased': [349], 'knowledge': [350, 435, 495], 'its': [356], 'biological': [357], 'functions': [358], 'new': [360, 531], 'without': [364, 789, 1055, 1380], 'agonist': [365, 647], 'activity': [366, 522, 846, 1369, 1427, 1592], 'was': [367, 404, 1862], 'more': [371], 'potent': [372, 1432], 'inhibition': [373], 'receptor.': [377], 'Randomized': [378], 'metastatic,': [384], 'resistant': [386, 458], 'showed': [389], 'significant': [390], 'survival': [391, 544, 868, 1348], 'benefits,': [392], 'enzalutamide': [399, 1269, 1350], 'August': [401], '2012.': [402, 727], 'Apalutamide': [403, 864], 'recently': [405], 'approved': [406, 412], 'while': [407], 'darolutamide': [408], 'is': [409], 'not': [410], 'yet': [411], 'United': [415], 'States.': [416], 'These': [417], 'next': [418], 'are': [421], 'being': [422], 'actively': [423], 'tested': [424], 'earlier': [426, 533], 'disease': [427, 466], 'states': [428, 467], 'such': [429], 'as': [430, 461, 463], 'nonmetastatic': [431, 456, 1183, 1439], 'Evolving': [434], 'resistance': [437, 957, 1000], 'mechanisms': [438], 'targeted': [442], 'treatments': [443], 'will': [444, 468, 509], 'stimulate': [445], 'research': [446], 'discovery': [449, 512], 'additional': [451], 'compounds.': [452], 'Further': [453], 'testing': [454], 'well': [462], 'sensitive': [465], 'hopefully': [469], 'augment': [470], 'our': [471], 'ability': [472], 'treat': [474], 'broader': [476], 'spectrum': [477], 'Conclusions:': [483], 'already': [486], 'provided': [487], 'treatment.': [493], 'Greater': [494], 'about': [496], 'structural': [498], 'functional': [500], 'biology': [501], 'facilitate': [510], 'further': [511, 516, 541], 'improved': [517], 'enhanced': [520], 'advanced': [526, 835, 1083, 1185, 1219, 1238, 1535, 1572, 1611], 'metastatic': [527, 580, 665, 891, 1058, 1126, 1156, 1216, 1275, 1332, 1374, 1463], 'disease.': [528, 1638], 'Testing': [529], 'these': [530], 'agents': [532], 'course': [536], 'may': [540], 'improve': [542], 'quality': [546], 'life': [548], 'current': [552], 'local': [553], 'and/or': [554, 1880, 1946], 'systemic': [555], 'modalities.': [557], 'References': [558], '1': [559, 899, 1470], ':': [560, 592, 607, 635, 659, 675, 689, 708, 731, 749, 765, 781, 805, 826, 844, 863, 881, 915, 937, 954, 972, 991, 1016, 1035, 1050, 1072, 1093, 1121, 1144, 1174, 1200, 1229, 1264, 1292, 1311, 1329, 1346, 1365, 1394, 1418, 1451, 1479, 1491, 1522, 1566, 1588, 1604, 1624, 1647, 1665], 'Studies': [561], 'prostatic': [563, 640, 681, 792, 1536], 'I.': [565], 'effect': [567, 1493], 'castration,': [569], 'estrogen': [571], 'injection': [575], 'serum': [577], 'phosphatases': 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'Edited': [623], '.': [625], 'Philadelphia:': [626], 'Lippincott': [627], 'Williams': [628], '&': [629, 1838], 'Wilkins1985:': [630], '193.': [631], '4': [634], 'New': [636, 916, 1856], 'hormonal': [637], 'therapy': [638, 1037, 1081], 'carcinoma:': [641], 'LHRH': [646, 769], 'antiandrogen.': [650], 'Clin': [651, 1114, 1304, 1386, 1411, 1676], 'Invest': [652], 'Med1982;': [653], '5:': [654], '267.': [655], '5': [658], 'changing': [661], 'natural': [662], 'history': [663], 'J2013;': [669], '19:': [670], '19.': [671, 1487], '6': [674], 'Selective': [676], 'retention': [677], 'dihydrotestosterone': [679], 'nuclei.': [682], 'Nature1968;': [683], '219:': [684], '277.': [685], '7': [688], 'intranuclear': [691], 'binding': [692], 'testosterone': [694, 712], '5-alpha-androstan-17-beta-ol-3-one': [696, 714], 'rat': [698, 716, 740], 'J': [700, 723, 742, 758, 774, 796, 874, 984, 1063, 1113, 1166, 1192, 1303, 1322, 1339, 1358, 1410, 1514, 1558, 1580, 1596, 1616, 1639, 1655], 'Biol': [701, 724], 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'possible': [814], 'cure': [815], 'localized': [817, 1235], 'cancer?.': [819], 'Urology2002;': [820], '60:': [821], '115.': [822], '14': [825], 'Development': [827], 'second-generation': [830], 'antiandrogen': [831], 'Science2009;': [838], '324:': [839], '787.': [840], '15': [843], 'Antitumour': [845], 'MDV3100': [848], 'castration-resistant': [850, 892, 1297, 1317, 1375, 1407, 1440, 1464], 'cancer:': [852, 923, 939, 1040, 1128, 1187, 1240, 1299, 1466, 1537], 'phase': [854, 898, 903, 1282, 1469, 1543], '1-2': [855], 'study.': [856, 1111, 1135, 1284, 1471], 'Lancet2010;': [857], '375:': [858], '1437.': [859], '16': [862], 'metastasis-free': [867], 'Med2018;': [875, 1323], '378:': [876, 1324], '1408.': [877], '17': [880, 1631], 'Activity': [882], 'ODM-201': [886, 1458], 'progressive': [890], '(ARADES):': [895], 'open-label': [897, 1468], 'dose-escalation': [900], 'randomised': [902, 1202], 'dose': [905], 'expansion': [906], 'trial.': [907, 1302], 'Lancet': [908, 1285], 'Oncol2014;': 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