Treatment for Advanced Tumors: Src Reclaims Center Stage

Name: Work Video:
Duration: 3 min 30 s
Justin M. Summy; Gary E. Gallick
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'SH2,': [99], 'SH3,': [100], 'SH1': [102], 'or': [103, 411, 868, 1401, 1743], 'tyrosine': [105, 117, 1024], 'domain.': [107], 'Critical': [108], 'COOH-terminal': [116, 216], '(Y530)': [118], 'that,': [119], 'when': [120], 'phosphorylated': [121, 217], 'by': [122, 138, 144, 171, 300, 306, 751, 989, 1095, 1315], 'C-terminal': [123], '(Csk),': [126], 'leads': [127, 844, 942], 'more': [130, 412, 557, 567, 1605, 1610, 1734], 'inactive': [131], 'conformation,': [133], 'as': [134, 271, 287, 289, 395, 487, 498, 500, 653, 900, 956, 1221, 1420, 1522, 1596, 1614, 1689, 1691, 1753], 'has': [135, 209, 1014, 1065, 1225, 1320], 'been': [136, 1015, 1321, 1470], 'shown': [137, 728, 784, 1226, 1322], 'numerous': [139, 223, 1389], 'molecular': [140], 'studies': [141, 165, 528, 853, 1369, 1705], 'confirmed': [143], 'crystal': [145], 'structures': [146, 594], '(5).': [147], 'An': [148], 'autophosphorylation': [149, 241], 'site': [150, 1204], '(Y418)': [151], 'indicative': [153], 'of,': [154], 'but': [155, 1508], 'not': [156, 480, 1805], 'entirely': [157], 'diagnostic': [158], 'for,': [159], 'activation.': [161], 'Biochemical': [162], 'structural': [164, 254], 'have': [166, 523, 727, 783, 981, 1105, 1189, 1468], 'discerned': [167], 'general': [169], 'mechanism': [170], 'which': [172, 204, 761, 1639], 'activity': [174, 335, 426, 436, 445, 622, 915, 921, 952, 1227, 1277, 1328], 'regulated': [176], '(6).A': [177], 'myriad': [178], 'stimuli,': [181], 'polypeptide': [183], 'growth': [184, 316, 383, 700, 722, 735, 1125], 'factors,': [185], 'hormones,': [186], 'integrin': [187, 389, 592, 615], 'aggregation,': [188], 'stress,': [189], 'cell': [190, 874, 975, 1241, 1249, 1312], 'cycle': [191, 960, 988, 1114, 1242], 'progression,': [192, 430], 'undoubtedly': [194, 1622], 'others,': [195], 'lead': [196, 402], 'phosphorylation': [199, 301], 'signaling': [201, 256, 279, 325], 'proteins': [202, 224, 656], 'SH2': [207, 246, 605], 'higher': [210], 'affinity': [211], 'than': [212, 1301, 1609], 'its': [214, 245, 680, 818, 1751], 'own': [215], 'thus': [220, 980, 1210], 'associates': [221, 252], 'with': [222, 253, 431, 570, 588, 765, 947, 986, 1110, 1216, 1416, 1443, 1472, 1706, 1748, 1786], '(depending': [225], 'on': [226, 303, 474, 771, 838, 936, 1020, 1045, 1069, 1370, 1392, 1730], 'input': [228], 'signal)': [229], 'assumes': [231], 'an': [232, 793, 1077, 1297], 'active': [233], 'conformation': [234], 'through': [235, 835], 'phosphatase-mediated': [236], 'dephosphorylation': [237], 'Y530': [239], 'Y418.': [243], 'Through': [244], 'SH3': [248, 603], 'domains,': [249], 'further': [251, 1129, 1139], 'proteins,': [257, 328], 'resulting': [260, 929], 'complexes': [261, 286, 617, 659], "Src's": [265], 'diverse': [268, 339], 'processes,': [270, 1345], 'illustrated': [272], 'Fig.': [274, 418], '1.': [275, 419], 'Specificity': [276], 'stems': [280], 'from': [281, 1017, 1560, 1572], 'composition': [283], 'these': [285, 350, 421, 636, 658, 898, 948, 1482, 1533, 1637, 1709], 'well': [288, 499, 901, 1516, 1690], 'their': [290, 1380, 1780], 'duration': [291], 'subcellular': [293], 'may': [296, 347, 522, 675, 1032, 1603, 1662], 'be': [297, 447, 661, 676, 1348, 1354, 1404, 1537, 1545, 1590, 1604, 1623, 1647, 1712], 'influenced': [299], 'sites': [302, 637], 'mediated': [305], 'C,': [309], 'A,': [312], 'cdc2': [313], 'kinase,': [314, 400], 'factor': [317, 384, 701], 'receptors': [318, 385, 837, 935], '(7).': [319], 'In': [320, 548, 1056, 1234], 'turn,': [321], 'substrates': [323], 'include': [324], 'enzymes,': [326], 'cytoskeletal': [327], 'mitotic': [329], 'regulators,': [330], 'etc.': [331], '(8).Aberrantly': [332], 'high': [333, 494], 'seen': [337], 'cancers': [340], '(9).': [341], 'Although': [342], 'number': [344, 1407], 'mechanisms': [346], 'account': [348], 'increases,': [351], 'increased': [353, 589, 846, 931, 1473], 'transcription': [354, 750, 759], '(10)': [355], 'perhaps': [357], 'very': [358], 'rare': [359], 'activating': [360], 'mutations': [361], '(4),': [362], 'activation': [363, 404, 478, 554, 691, 746, 752, 843, 908], 'likely': [365, 1569, 1645], 'primarily': [366], 'consequence': [368], 'genetic': [370], 'epigenetic': [372, 422], 'alterations': [373, 387, 651], 'tumor': [375, 688, 721, 815, 873, 883, 910, 924, 974, 995, 1047, 1059, 1101, 1116, 1130, 1256, 1458, 1464, 1554, 1678, 1693], 'cells.': [376, 822, 918, 938], 'As': [377, 420, 881, 1486], 'examples,': [378], 'overexpression': [379, 396], 'mutation': [381], 'mediators,': [393], 'such': [394, 1220, 1595, 1613], 'focal': [398, 613], 'adhesion': [399, 593, 616], 'frequently': [401], 'deregulation': [408], 'one': [410], 'pathways': [415], 'depicted': [416], 'changes': [423, 566], 'accumulate,': [424], 'increases': [427, 926, 963], 'during': [428], 'cancer': [429, 546, 711, 863, 1311, 1667], 'highest': [433], 'expression': [434, 696, 718, 740, 810], 'and/or': [435], 'observed': [439], 'metastases': [441, 879, 1273], '(11,': [442], '12).': [443], 'can': [446, 506], 'predictive': [448, 662], 'poor': [450], 'prognosis': [451], '(13).': [452], 'Thus,': [453, 516, 1388], 'current': [454, 640, 1368, 1702], 'expectation': [455], 'inhibitors': [459, 521, 544, 798, 859, 1021, 1044, 1134, 1198, 1213, 1352, 1372, 1398, 1445, 1478, 1534, 1577], 'will': [460, 660, 1587, 1621, 1655, 1711, 1725], 'hold': [461], 'most': [463, 1632], 'promise': [464], 'later': [466], 'stage': [467, 1496, 1741], 'neoplasms,': [468], 'clinical': [470, 1027, 1193, 1390, 1489, 1530, 1585, 1723], 'trials': [471, 1391, 1415, 1490, 1531, 1567, 1586, 1724], 'focusing': [473], 'this': [475, 987, 1141], 'potential.': [476], 'always': [481], 'confined': [482], 'late-stage': [484], 'tumors,': [485], 'however,': [486, 1365], 'it': [488, 1346], 'occurs': [489, 634], 'colon': [491, 710, 862, 1330, 1425], 'polyps': [492], 'malignant': [495], 'potential': [496, 896, 966, 983, 1040, 1107, 1499, 1563], '(14)': [497], 'ulcerative': [502], 'colitis': [503], '(15)': [504], 'promote': [507, 687, 1128], 'hyperproliferation': [508], 'mouse': [510, 707, 861, 1262, 1333], 'models': [511, 535, 549, 708, 779, 864, 1263, 1286, 1334], 'skin': [513], 'carcinogenesis': [514], '(16).': [515], 'some': [518, 1650], 'malignancies,': [519], 'efficacy': [524, 1013, 1041, 1580], 'earlier-stage': [526], 'disease.Recent': [527], 'using': [529, 709, 854, 1532], 'vitro': [531, 1324], 'vivo': [534, 778], 'provide': [536], 'strong': [537], 'support': [538], 'use': [541], 'therapy.': [547], 'epithelial': [551], 'cancer,': [552, 1426], 'promotes': [555, 887, 961], 'migratory': [558, 895, 965], 'invasive': [560], 'phenotype,': [561], 'inducing': [562], 'morphologic': [563], 'biochemical': [565], 'commonly': [568], 'associated': [569, 587, 1471], 'fibroblasts': [571], 'cells': [573, 816, 840, 899, 911, 925, 955, 971, 999, 1010, 1050, 1102, 1117, 1284, 1459, 1465, 1480, 1688, 1694], 'mesenchymal': [575], 'origin': [576], '(17),': [577], 'often': [578], 'termed': [579], 'epidermal': [580], 'mesenchymal–like': [582], 'transition.': [583], 'This': [584, 939, 958], 'phenotype': [585, 890], 'formation': [590, 610], 'decreased': [596], 'E-cadherin–mediated': [597], 'cell-cell': [598], 'contacts': [599], '(18).': [600], 'Intact': [601], 'domains': [606], 'essential': [608, 1078], 'adhesion–like': [614], '(19),': [618], 'catalytic': [621], 'important': [624, 802, 1606, 1802], 'dynamic': [627], 'modulation': [628], '(including': [629], 'elongation': [630], 'retraction)': [632], '(20).': [638], 'A': [639, 1406], 'area': [641], 'intense': [643], 'investigation': [644], 'proteomic': [646], 'analysis': [647], 'whether': [649], 'specific': [650, 1447], '(such': [652], 'phosphorylation)': [654], 'markers': [663], 'patient': [665], 'response': [666], 'inhibitors.Another': [669, 1036], 'key': [670], 'exploited': [677], 'therapeutically': [678], 'angiogenic': [684], 'factors': [685, 770, 1126], 'progression.': [689], 'hypoxia-mediated': [695], 'vascular': [698], 'endothelial': [699, 821, 839, 849, 892, 917, 937, 954, 970, 998, 1009], '(VEGF;': [702], 'ref.': [703], '21),': [704], 'cells,': [712, 850, 884, 893, 1060], 'inhibition': [713, 787, 1307], 'inhibits': [716, 1268], 'VEGF': [717, 737, 748, 773, 834, 836, 927, 934], 'limits': [720], '(22).': [723], 'More': [724], 'recently,': [725], 'we': [726, 782], 'regulates': [731, 913], 'both': [732, 994, 1046, 1100, 1718], 'constitutive': [733], 'factor–induced': [736], 'interleukin-8': [739], '(23,': [741], '24)': [742], 'up-regulates': [747], 'mRNA': [749], 'signal': [754, 1575], 'transducers': [755], 'activators': [757], '3,': [760], 'forms': [762], 'complex': [764], 'hypoxia-inducible': [766], 'factor-1': [767], 'other': [769, 1360, 1432, 1574], 'promoter': [774], '(25).': [775], 'Using': [776], 'effectively': [788], 'blocks': [789], 'neovascularization': [790], '(26),': [791], 'suggesting': [792], 'antiangiogenic': [794], 'clinic.Equally': [801], 'promoting': [809, 830, 1118], 'proangiogenic': [812], 'molecules': [813], 'members': [825, 1362], 'obligatory': [827], 'intermediates': [828], 'biological': [831, 991], 'functions': [832, 992, 1098], '(27).': [841], 'permeability': [847, 968], 'recent': [852, 1018], 'src−/−': [855], 'mice': [856], 'show': [865, 1384], 'abolishing': [867], 'reducing': [869], 'expression/activity': [871], 'decreases': [872], 'extravasation,': [875], 'thereby': [876], 'decreasing': [877], 'experimental': [878], '(28).': [880], 'activated': [885], 'mesenchymal-like': [889], 'increasing': [894, 950], '(29).': [902], 'Current': [903], 'results': [904], 'therefore': [905], 'suggest': [906], 'indirectly': [912], 'Increased': [919], 'expression,': [928], 'binding': [932], 'process': [940], 'then': [941], 'association': [944], 'receptors,': [949], 'well.': [957], 'continuing': [959], 'Src-mediated': [962, 1097], 'facilitates': [973], 'extravasation.': [976], 'Inhibitors': [977], 'interfere': [985, 1109], 'affecting': [990, 1096], 'tumor-associated': [997, 1008], 'contribute': [1001], 'metastasis.': [1003], 'importance': [1005, 1682], 'targeting': [1007, 1684], 'therapeutic': [1012, 1755], 'highlighted': [1016], 'work': [1019, 1721, 1803], 'receptor': [1023], 'trial': [1028], '(30–35);': [1029], 'similar': [1030], 'principles': [1031], 'apply': [1033], 'example': [1037], 'normal': [1049, 1081], 'treating': [1053], 'bone': [1054, 1089, 1119, 1161], 'metastases.': [1055], 'cultured': [1057], 'prostate': [1058, 1255], 'inhibitor,': [1063, 1149], 'dasatinib,': [1064], 'expected': [1067, 1349], 'effects': [1068], 'suppressing': [1070], 'tumorigenic': [1071], 'properties': [1072, 1253], '(36).': [1073], 'also': [1075, 1212], 'osteoclast': [1082, 1155], 'absolutely': [1086], 'resorption,': [1090], 'however': [1091], '(37).': [1092], 'inhibitors,': [1094, 1168, 1708], 'osteoclasts,': [1104], 'well-described': [1112], 'vicious': [1113], 'destruction': [1120], 'turn': [1123], 'yields': [1124], 'growth.': [1131], 'Bone-targeted': [1132], 'being': [1136, 1412], 'developed': [1137], 'test': [1140], 'possibility.11Tomi': [1142], 'K.': [1143], 'Sawyer,': [1144], 'personal': [1145, 1165, 1520], 'communication.': [1146, 1521], 'Src-selective': [1148, 1351, 1660], 'AZD': [1150], '0530,': [1151], 'does': [1152], 'indeed': [1153], 'affect': [1154], 'humans,': [1158], 'inhibiting': [1159], 'osteoclastic': [1160], 'resorption.22Tim': [1162], 'P.': [1163], 'Green,': [1164], 'communication.Currently,': [1166], 'dasatinib': [1169, 1236, 1513], '(BMS354825;': [1170], 'Bristol': [1171], 'Meyers': [1172], 'Squibb': [1173], 'Oncology,': [1174], 'Princeton,': [1175], 'NY),': [1176, 1188], 'AZD-0530': [1177], '(AstraZeneca,': [1178], 'Macclesfield,': [1179], 'United': [1180], 'Kingdom),': [1181], 'SKI-606': [1183], '(Wyeth': [1184], 'Research,': [1185], 'Pearl': [1186], 'River,': [1187], 'reached': [1190], 'phase': [1191, 1510, 1565], '1': [1192], 'trials.': [1194], 'small': [1196], 'molecule': [1197], 'directed': [1200], 'ATP-binding': [1203], 'closely': [1217], 'related': [1218], 'structure,': [1219], 'Abl.': [1222], 'inhibitor': [1224, 1318, 1419, 1506], 'against': [1228, 1282, 1329, 1382], 'preclinical': [1231], 'studies,': [1232], 'however.': [1233], 'vitro,': [1235], 'suppresses': [1237], 'invasion': [1238, 1288], 'induces': [1240], 'arrest': [1243], 'head': [1245], 'neck': [1247], 'squamous': [1248], 'carcinomas': [1250], '(38),': [1251], 'affects': [1252], 'progression': [1257, 1555], '(36)': [1258], 'orthotopic': [1261], 'pancreatic': [1265, 1457], 'carcinoma,': [1266], 'greatly': [1267], 'development': [1270], 'liver': [1272], '(39).': [1274], 'AZD0530': [1275, 1319], 'shows': [1276, 1327], 'nanomolar': [1280], 'level': [1281], 'v-Src–transformed': [1283], 'supporting': [1291], 'hypothesis': [1293], 'anti-invasive': [1298], 'target': [1299, 1756], 'rather': [1300], 'direct': [1303], 'antiproliferative': [1304], 'target.': [1305], 'Dramatic': [1306], 'human': [1309], 'breast': [1310], '(MDA-MB231)': [1313], 'migration': [1314], '(40).': [1325], 'SKI606': [1326], 'tumors': [1331], '(41).Given': [1335], 'involved': [1339], 'so': [1341], 'many': [1342, 1573, 1796], 'fundamental': [1343], 'might': [1347], 'would': [1353], 'toxic.': [1355], 'Knockouts': [1356], 'viable,': [1364], '(42),': [1366], 'Src/Abl': [1371], 'chronic': [1374, 1451], 'myelogenous': [1375, 1452], 'leukemia': [1376, 1453], 'patients': [1377, 1454], '(used': [1378], 'effectiveness': [1381, 1500], 'Bcr-Abl)': [1383], 'only': [1385], 'limited': [1386], 'toxicity.': [1387], 'each': [1393], 'previously': [1396], 'described': [1397], 'ongoing': [1400, 1488, 1529, 1561, 1719], 'soon': [1402], 'initiated.': [1405], 'different': [1409], 'strategies': [1410], 'used,': [1413], 'single': [1421], 'agent': [1422], 'metastatic': [1424, 1674], 'various': [1429], 'combinations': [1430, 1439], 'solid': [1433, 1633, 1758], 'tumors.': [1434, 1448, 1634], 'Recent': [1435], 'evidence': [1436], 'suggests': [1437], 'logical': [1438], 'chemotherapeutic': [1441, 1484], 'agents': [1442, 1661], 'Some': [1449], 'gleevec-resistant': [1450], '(43),': [1455], 'gemcitabine-resistant': [1456], '(44),': [1460], 'taxol-resistant': [1462], 'ovarian': [1463], '(45,': [1466], '46)': [1467], 'all': [1469], 'activation,': [1475], 'sensitize': [1479], 'standard': [1483], 'agents.': [1485], 'yet,': [1487], 'too': [1493], 'early': [1494], 'determine': [1498, 1726], 'any': [1502], 'trials,': [1507, 1512], 'I': [1511], 'seems': [1514], 'generally': [1515], 'tolerated33Faye': [1517], 'M.': [1518], 'Johnson,': [1519], 'AZD0530.2Although': [1524], 'successes': [1526], 'remain': [1535], 'determined,': [1538], 'definition': [1540], 'success': [1542, 1716], 'needs': [1543], 'considered': [1546], 'carefully.': [1547, 1592], 'Given': [1548], 'roles': [1550], 'metastasis,': [1557], 'expectations': [1559], 'future': [1564], 'II/III': [1566], 'differ': [1571], 'transduction-targeted': [1576], 'end': [1581], 'points': [1582], 'need': [1588], 'chosen': [1591], 'End': [1593], 'points,': [1594], 'disease': [1597], 'stabilization': [1598], 'time': [1600], 'recurrence,': [1602], 'assess': [1608], 'classic': [1611], 'measures,': [1612], 'partial': [1615], 'complete': [1617, 1642], 'remission.': [1618], 'Old': [1619], 'lessons': [1620], 'relearned,': [1624], 'fallibility': [1627], 'single-agent': [1629], 'therapy': [1630, 1738], 'Toxicities': [1635], 'agents,': [1638], 'still': [1640], 'lack': [1641], 'selectivity,': [1643], 'problematic': [1648], 'patients,': [1651], 'drug': [1653], 'resistance': [1654], 'almost': [1656], 'assuredly': [1657], 'arise.': [1658], 'Nevertheless,': [1659], 'advance': [1663], 'new': [1664], 'concepts': [1665], 'therapy,': [1668], 'how': [1670], 'better': [1672], 'limit': [1673], 'spread': [1675], 'without': [1676], 'eradicating': [1677], 'growth,': [1679], 'host': [1686], 'stromal': [1687], 'themselves': [1695], 'achieve': [1697], 'efficacy.': [1698], 'Because': [1699], 'flurry': [1703], 'predictions': [1710], 'tested': [1713], 'rapidly.': [1714], 'laboratory': [1720], 'if': [1727], 'remains': [1729], 'center': [1731], 'stage,': [1732], 'stimulates': [1733], 'imaginative': [1735], 'approaches': [1736], 'advanced': [1740], 'disease,': [1742], 'returns': [1744], 'wings': [1747], 'respect': [1749, 1787], 'relevance': [1752], 'tumors.We': [1759], 'thank': [1760], 'Victor': [1761], 'A.': [1762], 'Levin,': [1763], 'MD;': [1764, 1768], 'James': [1765], 'L.': [1766], 'Abbruzzese,': [1767], 'Jan': [1769], 'C.': [1770], 'Liang,': [1771], 'PhD;': [1772], 'Isaiah': [1774], 'J.': [1775], 'Fidler,': [1776], 'DVM,': [1777], 'PhD': [1778], 'reading': [1782], 'insightful': [1784], 'suggestions': [1785], 'article.': [1790], 'authors': [1792], 'apologize': [1793], 'workers': [1797], 'field': [1800], 'whose': [1801], 'was': [1804], 'cited': [1806], 'due': [1807], 'space': [1809], 'limitations.': [1810]}, 'cited_by_api_url': 'https://api.openalex.org/works?filter=cites:W2136929338', 'counts_by_year': [{'year': 2024, 'cited_by_count': 1}, {'year': 2023, 'cited_by_count': 15}, {'year': 2022, 'cited_by_count': 4}, {'year': 2021, 'cited_by_count': 8}, {'year': 2020, 'cited_by_count': 4}, {'year': 2019, 'cited_by_count': 5}, {'year': 2018, 'cited_by_count': 9}, {'year': 2017, 'cited_by_count': 10}, {'year': 2016, 'cited_by_count': 5}, {'year': 2015, 'cited_by_count': 10}, {'year': 2014, 'cited_by_count': 10}, {'year': 2013, 'cited_by_count': 15}, {'year': 2012, 'cited_by_count': 16}], 'updated_date': '2025-01-02T01:27:45.592566', 'created_date': '2016-06-24'}
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